{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:18:18Z","timestamp":1792498698819,"version":"4.5.0"},"reference-count":233,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Cognitive decline represents one of the most common clinical manifestations of neurodegenerative diseases (NDs), substantially affecting the quality of life of both patients and their families. Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis are major NDs characterized by a progressive degeneration of the central nervous system, with functional impairments extending beyond motor symptoms to multiple cognitive domains, including memory, attention, language, and executive functions. Increasing evidence highlights misfolded protein accumulation as a key driver of neuronal dysfunction and cognitive deterioration. This narrative review examines the major cognitive deficits associated with these disorders, focusing on the underlying molecular mechanisms, particularly protein aggregation, as well as clinical manifestations and their effects on daily life. Furthermore, current diagnostic tools and emerging therapeutic options for mitigating cognitive decline will be further discussed.<\/jats:p>","DOI":"10.3390\/neurolint18030048","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:48:56Z","timestamp":1772542136000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0631-3676","authenticated-orcid":false,"given":"Elisa","family":"Duranti","sequence":"first","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2730-5974","authenticated-orcid":false,"given":"Chiara","family":"Villa","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Far\u00ec, G., Lunetti, P., Pignatelli, G., Raele, M.V., Cera, A., Mintrone, G., Ranieri, M., Megna, M., and Capobianco, L. (2021). The Effect of Physical Exercise on Cognitive Impairment in Neurodegenerative Disease: From Pathophysiology to Clinical and Rehabilitative Aspects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111632"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2022). Molecular Investigations of Protein Aggregation in the Pathogenesis of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010704"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2024). From Brain to Muscle: The Role of Muscle Tissue in Neurodegenerative Disorders. Biology, 13.","DOI":"10.3390\/biology13090719"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101939","DOI":"10.1016\/j.arr.2023.101939","article-title":"The multifactorial nature of healthy brain ageing: Brain changes, functional decline and protective factors","volume":"88","author":"Turrini","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1586\/ern.11.155","article-title":"Distinguishing Alzheimer\u2019s disease from other major forms of dementia","volume":"11","author":"Karantzoulis","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1136\/jnnp.2005.083113","article-title":"Neuropsychiatric symptoms in patients with Parkinson\u2019s disease and dementia: Frequency, profile and associated care giver stress","volume":"78","author":"Aarsland","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1212\/WNL.0b013e31828f18ac","article-title":"Cognitive changes predict functional decline in ALS: A population-based longitudinal study","volume":"80","author":"Elamin","year":"2013","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1212\/01.wnl.0000172911.39167.b6","article-title":"Prevalence and patterns of cognitive impairment in sporadic ALS","volume":"65","author":"Ringholz","year":"2005","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-\u03b2 Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1186\/s12964-024-01791-8","article-title":"Misfolding and aggregation in neurodegenerative diseases: Protein quality control machinery as potential therapeutic clearance pathways","volume":"22","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Plascencia-Villa, G., and Perry, G. (2023). Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer\u2019s Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12081628"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hu, C., Lin, M., Wang, C., and Zhang, S. (2025). Current Understanding of Protein Aggregation in Neurodegenerative Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110568"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1136\/jnnp.2008.154146","article-title":"Memory performance is related to amyloid and tau pathology in the hippocampus","volume":"80","author":"Reitz","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/alz.13355","article-title":"The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline","volume":"20","author":"Boccalini","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41531-024-00708-z","article-title":"Misfolded protein deposits in Parkinson\u2019s disease and Parkinson\u2019s disease-related cognitive impairment, a [(11)C]PBB3 study","volume":"10","author":"Matarazzo","year":"2024","journal-title":"NPJ Parkinsons Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.14336\/AD.2019.1120","article-title":"Emotional Lability at Disease Onset Is an Independent Prognostic Factor of Faster Disease Progression in Amyotrophic Lateral Sclerosis","volume":"11","author":"Szacka","year":"2020","journal-title":"Aging Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ciechanover, A., and Kwon, Y.T. (2017). Protein Quality Control by Molecular Chaperones in Neurodegeneration. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00185"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Brezic, N., Gligorevic, S., Sic, A., and Knezevic, N.N. (2025). Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040259"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1742-4658.2011.08456.x","article-title":"Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation","volume":"279","author":"Kriegenburg","year":"2012","journal-title":"FEBS J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ajmal, M.R. (2023). Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response. Diseases, 11.","DOI":"10.3390\/diseases11010030"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Michalska, P., and Le\u00f3n, R. (2020). When It Comes to an End: Oxidative Stress Crosstalk with Protein Aggregation and Neuroinflammation Induce Neurodegeneration. Antioxidants, 9.","DOI":"10.3390\/antiox9080740"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dantuma, N.P., and Bott, L.C. (2014). The ubiquitin-proteasome system in neurodegenerative diseases: Precipitating factor, yet part of the solution. Front. Mol. Neurosci., 7.","DOI":"10.3389\/fnmol.2014.00070"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e161","DOI":"10.1002\/mco2.161","article-title":"Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Alharbi, B.M., Albinhassan, T.H., Alzahrani, R.A., Bouchama, A., Mohammad, S., Alomari, A.A., Bin-Jumah, M.N., AlSuhaibani, E.S., and Malik, S.S. (2023). Profiling the Hsp70 Chaperone Network in Heat-Induced Proteotoxic Stress Models of Human Neurons. Biology, 12.","DOI":"10.3390\/biology12030416"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-biochem-060208-092442","article-title":"Molecular chaperone functions in protein folding and proteostasis","volume":"82","author":"Kim","year":"2013","journal-title":"Annu. Rev. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kohler, V., and Andr\u00e9asson, C. (2023). Reversible protein assemblies in the proteostasis network in health and disease. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1155521"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1159\/000225957","article-title":"The shock of aging: Molecular chaperones and the heat shock response in longevity and aging\u2014A mini-review","volume":"55","author":"Calderwood","year":"2009","journal-title":"Gerontology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3109\/02656736.2013.798873","article-title":"Stress proteins in aging and life span","volume":"29","author":"Murshid","year":"2013","journal-title":"Int. J. Hyperth."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12079-014-0243-9","article-title":"Heat shock proteins in neurodegenerative disorders and aging","volume":"8","author":"Leak","year":"2014","journal-title":"J. Cell Commun. Signal"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/cvr\/cvu003","article-title":"Desmin modifications associate with amyloid-like oligomers deposition in heart failure","volume":"102","author":"Agnetti","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/prca.201400037","article-title":"Protein post-translational modifications and misfolding: New concepts in heart failure","volume":"8","author":"Agnetti","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vogt, A.S., Jennings, G.T., Mohsen, M.O., Vogel, M., and Bachmann, M.F. (2023). Alzheimer\u2019s Disease: A Brief History of Immunotherapies Targeting Amyloid \u03b2. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043895"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Penke, B., Bog\u00e1r, F., and F\u00fcl\u00f6p, L. (2017). \u03b2-Amyloid and the Pathomechanisms of Alzheimer\u2019s Disease: A Comprehensive View. Molecules, 22.","DOI":"10.3390\/molecules22101692"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.1021\/bi300316d","article-title":"A mass spectrometric approach for characterization of amyloid-\u03b2 aggregates and identification of their post-translational modifications","volume":"51","author":"Tay","year":"2012","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/alzrt258","article-title":"Truncated and modified amyloid-beta species","volume":"6","author":"Kummer","year":"2014","journal-title":"Alzheimers Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","article-title":"Tau protein isoforms, phosphorylation and role in neurodegenerative disorders","volume":"33","author":"Delacourte","year":"2000","journal-title":"Brain Res. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Duranti, E., and Villa, C. (2024). Insights into Dysregulated Neurological Biomarkers in Cancer. Cancers, 16.","DOI":"10.3390\/cancers16152680"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbadis.2004.08.010","article-title":"Tau gene alternative splicing: Expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases","volume":"1739","author":"Andreadis","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/0896-6273(89)90077-9","article-title":"Developmentally regulated expression of specific tau sequences","volume":"2","author":"Kosik","year":"1989","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1002\/alz.13784","article-title":"The six brain-specific TAU isoforms and their role in Alzheimer\u2019s disease and related neurodegenerative dementia syndromes","volume":"20","author":"Buchholz","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s40478-019-0823-2","article-title":"A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer\u2019s disease brain","volume":"7","author":"Ehrig","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.tins.2022.01.006","article-title":"How do protein aggregates escape quality control in neurodegeneration?","volume":"45","author":"Koopman","year":"2022","journal-title":"Trends Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1176\/jnp.14.2.223","article-title":"An essay on the shaking palsy","volume":"14","author":"Parkinson","year":"2002","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13024-021-00501-z","article-title":"Neuropathology and molecular diagnosis of Synucleinopathies","volume":"16","author":"Koga","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00401-011-0852-9","article-title":"Neuropathology underlying clinical variability in patients with synucleinopathies","volume":"122","author":"Halliday","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1124\/pharmrev.123.001111","article-title":"Posttranslational Modifications of \u03b1-Synuclein, Their Therapeutic Potential, and Crosstalk in Health and Neurodegenerative Diseases","volume":"76","author":"Hassanzadeh","year":"2024","journal-title":"Pharmacol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"ref_54","first-page":"519","article-title":"SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology","volume":"21","author":"Saccon","year":"2014","journal-title":"Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108701","DOI":"10.1016\/j.abb.2020.108701","article-title":"SOD1, more than just an antioxidant","volume":"697","author":"Eleutherio","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.redox.2019.101270","article-title":"Mechanisms of SOD1 regulation by post-translational modifications","volume":"26","author":"Banks","year":"2019","journal-title":"Redox Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.adgen.2015.07.001","article-title":"Functional Significance of TDP-43 Mutations in Disease","volume":"91","author":"Buratti","year":"2015","journal-title":"Adv. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cordts, I., Wachinger, A., Scialo, C., Lingor, P., Polymenidou, M., Buratti, E., and Feneberg, E. (2023). TDP-43 Proteinopathy Specific Biomarker Development. Cells, 12.","DOI":"10.3390\/cells12040597"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"56612","DOI":"10.18632\/oncotarget.17979","article-title":"TDP-43\/HDAC6 axis promoted tumor progression and regulated nutrient deprivation-induced autophagy in glioblastoma","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Chen, H.J., and Mitchell, J.C. (2021). Mechanisms of TDP-43 Proteinopathy Onset and Propagation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116004"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/s12276-020-00513-7","article-title":"The role of TDP-43 propagation in neurodegenerative diseases: Integrating insights from clinical and experimental studies","volume":"52","author":"Jo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/WCO.0b013e3283168d1d","article-title":"The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"21","author":"Mackenzie","year":"2008","journal-title":"Curr. Opin. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13024-020-00397-1","article-title":"The role of TDP-43 mislocalization in amyotrophic lateral sclerosis","volume":"15","author":"Suk","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13024-023-00608-5","article-title":"The era of cryptic exons: Implications for ALS-FTD","volume":"18","author":"Mehta","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1126\/science.aab0983","article-title":"TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD","volume":"349","author":"Ling","year":"2015","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41593-018-0300-4","article-title":"ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair","volume":"22","author":"Klim","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41593-018-0293-z","article-title":"Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration","volume":"22","author":"Melamed","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41586-022-04424-7","article-title":"TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A","volume":"603","author":"Ma","year":"2022","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/cge.13015","article-title":"The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis","volume":"92","author":"Liu","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrneurol.2014.78","article-title":"The role of FUS gene variants in neurodegenerative diseases","volume":"10","author":"Deng","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.conb.2011.05.029","article-title":"Understanding the role of TDP-43 and FUS\/TLS in ALS and beyond","volume":"21","author":"Cleveland","year":"2011","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1212\/WNL.0000000000003067","article-title":"Comparative analysis of C9orf72 and sporadic disease in an ALS clinic population","volume":"87","author":"Umoh","year":"2016","journal-title":"Neurology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S1474-4422(12)70014-5","article-title":"Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: A population-based cohort study","volume":"11","author":"Byrne","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e670","DOI":"10.1212\/NXG.0000000000000670","article-title":"Expanding Clinical Spectrum of C9ORF72-Related Disorders and Promising Therapeutic Strategies: A Review","volume":"8","author":"Breevoort","year":"2022","journal-title":"Neurol. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"180138","DOI":"10.1098\/rsob.180138","article-title":"Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: An overview of induced pluripotent stem-cell-based disease models","volume":"8","author":"Taoufik","year":"2018","journal-title":"Open Biol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gutierrez, B.A., and Limon, A. (2022). Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer\u2019s and Parkinson\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071743"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ribari\u010d, S. (2023). Detecting Early Cognitive Decline in Alzheimer\u2019s Disease with Brain Synaptic Structural and Functional Evaluation. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020355"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Meftah, S., and Gan, J. (2023). Alzheimer\u2019s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front. Synaptic Neurosci., 15.","DOI":"10.3389\/fnsyn.2023.1129036"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"110217","DOI":"10.1016\/j.neuropharm.2024.110217","article-title":"Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis","volume":"264","author":"Yu","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: Sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jocn.2009.05.006","article-title":"The role of microglia in central nervous system immunity and glioma immunology","volume":"17","author":"Yang","year":"2010","journal-title":"J. Clin. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Shao, F., Wang, X., Wu, H., Wu, Q., and Zhang, J. (2022). Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.825086"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1152\/physrev.00041.2013","article-title":"Astrocyte reactivity and reactive astrogliosis: Costs and benefits","volume":"94","author":"Pekny","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Peggion, C., Cal\u00ec, T., and Brini, M. (2024). Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?. Antioxidants, 13.","DOI":"10.3390\/antiox13020240"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.biopsych.2017.11.018","article-title":"Mitochondrial Etiology of Neuropsychiatric Disorders","volume":"83","author":"Pei","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"104892","DOI":"10.1016\/j.neubiorev.2022.104892","article-title":"Emerging roles of brain metabolism in cognitive impairment and neuropsychiatric disorders","volume":"142","author":"Morella","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.freeradbiomed.2022.09.032","article-title":"Altered glucose metabolism in Alzheimer\u2019s disease: Role of mitochondrial dysfunction and oxidative stress","volume":"193","author":"Dewanjee","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102667","DOI":"10.1016\/j.arr.2025.102667","article-title":"Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders","volume":"104","author":"Wen","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"132931","DOI":"10.1016\/j.neulet.2017.06.050","article-title":"Inflammation and mitochondrial dysfunction: A vicious circle in neurodegenerative disorders?","volume":"710","author":"Witte","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Angiulli, F., Conti, E., Zoia, C.P., Da Re, F., Appollonio, I., Ferrarese, C., and Tremolizzo, L. (2021). Blood-Based Biomarkers of Neuroinflammation in Alzheimer\u2019s Disease: A Central Role for Periphery?. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091525"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrn.2017.74","article-title":"Prefrontal-hippocampal interactions in episodic memory","volume":"18","author":"Eichenbaum","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_95","first-page":"161","article-title":"Temporal unfolding of declining episodic memory on the Free and Cued Selective Reminding Test in the predementia phase of Alzheimer\u2019s disease: Implications for clinical trials","volume":"10","author":"Grober","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1038\/s41598-022-17634-w","article-title":"Predicting real world spatial disorientation in Alzheimer\u2019s disease patients using virtual reality navigation tests","volume":"12","author":"Puthusseryppady","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lindsay, H., Tr\u00f6ger, J., and K\u00f6nig, A. (2021). Language Impairment in Alzheimer\u2019s Disease-Robust and Explainable Evidence for AD-Related Deterioration of Spontaneous Speech Through Multilingual Machine Learning. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.642033"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"105041","DOI":"10.1016\/j.bandl.2021.105041","article-title":"Language changes in Alzheimer\u2019s disease: A systematic review of verb processing","volume":"223","author":"Williams","year":"2021","journal-title":"Brain Lang."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1748-6653.2012.02038.x","article-title":"Cognitive and affective Theory of Mind in mild to moderate Alzheimer\u2019s disease","volume":"7","author":"Laisney","year":"2013","journal-title":"J. Neuropsychol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pneurobio.2014.02.004","article-title":"What is normal in normal aging? Effects of aging, amyloid and Alzheimer\u2019s disease on the cerebral cortex and the hippocampus","volume":"117","author":"Fjell","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Villa, C., and Stoccoro, A. (2022). Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer\u2019s Disease. Genes, 13.","DOI":"10.3390\/genes13081308"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Salvadores, N., Ger\u00f3nimo-Olvera, C., and Court, F.A. (2020). Axonal Degeneration in AD: The Contribution of A\u03b2 and Tau. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.581767"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41580-024-00753-9","article-title":"Cellular and pathological functions of tau","volume":"25","author":"Naguib","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1093\/cercor\/bhy152","article-title":"Spreading of Tau Pathology in Sporadic Alzheimer\u2019s Disease Along Cortico-cortical Top-Down Connections","volume":"28","author":"Braak","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Barmaki, H., Nourazarian, A., and Khaki-Khatibi, F. (2023). Proteostasis and neurodegeneration: A closer look at autophagy in Alzheimer\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1281338"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13024-023-00664-x","article-title":"Simple model systems reveal conserved mechanisms of Alzheimer\u2019s disease and related tauopathies","volume":"18","author":"Jiang","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1073\/pnas.242720499","article-title":"Chaperones increase association of tau protein with microtubules","volume":"100","author":"Dou","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Bohush, A., Bieganowski, P., and Filipek, A. (2019). Hsp90 and Its Co-Chaperones in Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20204976"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/0115672050301407240408033046","article-title":"Post-Translational Modifications in Tau and Their Roles in Alzheimer\u2019s Pathology","volume":"21","author":"Kalyaanamoorthy","year":"2024","journal-title":"Curr. Alzheimer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101208","DOI":"10.1016\/j.arr.2020.101208","article-title":"Synaptic basis of Alzheimer\u2019s disease: Focus on synaptic amyloid beta, P-tau and mitochondria","volume":"65","author":"John","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6555","DOI":"10.1038\/s41598-019-43076-y","article-title":"Synapse loss and progress of Alzheimer\u2019s disease -A network model","volume":"9","author":"Kashyap","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Dom\u00ednguez-\u00c1lvaro, M., Montero-Crespo, M., Blazquez-Llorca, L., DeFelipe, J., and Alonso-Nanclares, L. (2019). 3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer\u2019s Disease. eNeuro, 6.","DOI":"10.1523\/ENEURO.0140-19.2019"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ana.410300410","article-title":"Physical basis of cognitive alterations in Alzheimer\u2019s disease: Synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry","year":"1991","journal-title":"Ann. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41583-021-00531-y","article-title":"Super-resolution microscopy: A closer look at synaptic dysfunction in Alzheimer disease","volume":"22","author":"Padmanabhan","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Zhang, H., Jiang, X., Ma, L., Wei, W., Li, Z., Chang, S., Wen, J., Sun, J., and Li, H. (2022). Role of A\u03b2 in Alzheimer\u2019s-related synaptic dysfunction. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.964075"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s40478-021-01246-y","article-title":"Synaptic tau: A pathological or physiological phenomenon?","volume":"9","author":"Robbins","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 19, 1598\u20131695.","DOI":"10.1002\/alz.13016"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3233\/JAD-160612","article-title":"Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer\u2019s disease Neurons","volume":"57","author":"Rajmohan","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0002-9440(10)63436-0","article-title":"Synaptic changes in Alzheimer\u2019s disease: Increased amyloid-beta and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence","volume":"165","author":"Gylys","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"25424823251341870","DOI":"10.1177\/25424823251341870","article-title":"Dual impact of neuroinflammation on cognitive and motor impairments in Alzheimer\u2019s disease","volume":"9","author":"Fakorede","year":"2025","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Sharma, C., Kim, S., Nam, Y., Jung, U.J., and Kim, S.R. (2021). Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094850"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Misrani, A., Tabassum, S., and Yang, L. (2021). Mitochondrial Dysfunction and Oxidative Stress in Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.617588"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"14670","DOI":"10.1073\/pnas.0903563106","article-title":"Mitochondrial bioenergetic deficit precedes Alzheimer\u2019s pathology in female mouse model of Alzheimer\u2019s disease","volume":"106","author":"Yao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1586\/14737175.2015.1058160","article-title":"The role of mitochondrial disturbances in Alzheimer, Parkinson and Huntington diseases","volume":"15","author":"Carvalho","year":"2015","journal-title":"Expert Rev. Neurother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1083\/jcb.201709172","article-title":"Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases","volume":"216","author":"Kawamata","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2478\/jtim-2022-0024","article-title":"Aberrant Energy Metabolism in Alzheimer\u2019s Disease","volume":"10","author":"Yu","year":"2022","journal-title":"J. Transl. Int. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.bbabio.2014.02.007","article-title":"Mitochondrial import and degradation of amyloid-\u03b2 peptide","volume":"1837","author":"Pinho","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11033-023-09021-z","article-title":"Oxidative stress in Alzheimer\u2019s disease: Current knowledge of signaling pathways and therapeutics","volume":"51","author":"Dhapola","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Muleiro Alvarez, M., Cano-Herrera, G., Osorio Mart\u00ednez, M.F., Vega Gonzales-Portillo, J., Monroy, G.R., Murguiondo P\u00e9rez, R., Torres-R\u00edos, J.A., van Tienhoven, X.A., Garibaldi Bernot, E.M., and Esparza Salazar, F. (2024). A Comprehensive Approach to Parkinson\u2019s Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137183"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.parkreldis.2016.04.009","article-title":"Cognitive decline and quality of life in incident Parkinson\u2019s disease: The role of attention","volume":"27","author":"Lawson","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.gaitpost.2009.09.019","article-title":"Executive dysfunction and attention contribute to gait interference in \u2018off\u2019 state Parkinson\u2019s Disease","volume":"31","author":"Lord","year":"2010","journal-title":"Gait Posture"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Cammisuli, D.M., Pagni, C., Palermo, G., Frosini, D., Bonaccorsi, J., Radicchi, C., Cintoli, S., Tommasini, L., Tognoni, G., and Ceravolo, R. (2021). Mild Cognitive Impairment in de novo Parkinson\u2019s Disease: Selective Attention Deficit as Early Sign of Neurocognitive Decay. Front. Psychol., 12.","DOI":"10.3389\/fpsyg.2021.546476"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"963689720947416","DOI":"10.1177\/0963689720947416","article-title":"The Association Between Parkinson\u2019s Disease and Attention-Deficit Hyperactivity Disorder","volume":"29","author":"Fan","year":"2020","journal-title":"Cell Transplant."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e02031","DOI":"10.1002\/brb3.2031","article-title":"Components determining the slowness of information processing in parkinson\u2019s disease","volume":"11","author":"Arroyo","year":"2021","journal-title":"Brain Behav."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.parkreldis.2020.05.006","article-title":"Functional correlates of cognitive slowing in Parkinson\u2019s disease","volume":"76","author":"Grolez","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bjpt.2020.11.005","article-title":"Mild and marked executive dysfunction and falls in people with Parkinson\u2019s disease","volume":"25","author":"Pelicioni","year":"2021","journal-title":"Braz. J. Phys. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"108389","DOI":"10.1016\/j.neuropsychologia.2022.108389","article-title":"The impact of executive dysfunctions on Theory of Mind abilities in Parkinson\u2019s disease","volume":"176","author":"Maggi","year":"2022","journal-title":"Neuropsychologia"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1080\/23279095.2023.2256918","article-title":"Visuospatial memory profile of patients with Parkinson\u2019s disease","volume":"32","author":"Oliveira","year":"2025","journal-title":"Appl. Neuropsychol. Adult"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Nieto-Escamez, F., Obrero-Gait\u00e1n, E., and Cort\u00e9s-P\u00e9rez, I. (2023). Visual Dysfunction in Parkinson\u2019s Disease. Brain Sci., 13.","DOI":"10.3390\/brainsci13081173"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Cardinale, A., Calabrese, V., de Iure, A., and Picconi, B. (2021). Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126517"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/jnc.13570","article-title":"The contribution of alpha synuclein to neuronal survival and function\u2014Implications for Parkinson\u2019s disease","volume":"137","author":"Benskey","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1038\/emboj.2009.298","article-title":"Chaperone proteostasis in Parkinson\u2019s disease: Stabilization of the Hsp70\/alpha-synuclein complex by Hip","volume":"28","author":"Roodveldt","year":"2009","journal-title":"EMBO J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ijbiomac.2013.05.032","article-title":"Applying chaperones to protein-misfolding disorders: Molecular chaperones against \u03b1-synuclein in Parkinson\u2019s disease","volume":"60","author":"Chaari","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.4103\/1673-5374.300431","article-title":"Chaperone proteins as ameliorators of \u03b1-synuclein-induced synaptic pathologies: Insights into Parkinson\u2019s disease","volume":"16","author":"Banks","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1038\/ncomms4633","article-title":"MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration","volume":"5","author":"Zucca","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Pajares, M., I. Rojo, A., Manda, G., Bosc\u00e1, L., and Cuadrado, A. (2020). Inflammation in Parkinson\u2019s Disease: Mechanisms and Therapeutic Implications. Cells, 9.","DOI":"10.3390\/cells9071687"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/brain\/awt337","article-title":"Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson\u2019s disease with mild cognitive impairment","volume":"137","author":"Christopher","year":"2014","journal-title":"Brain"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrneurol.2017.27","article-title":"Cognitive decline in Parkinson disease","volume":"13","author":"Aarsland","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11910-013-0377-9","article-title":"Cholinergic dysfunction in Parkinson\u2019s disease","volume":"13","author":"Bohnen","year":"2013","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"103","DOI":"10.5607\/en.2015.24.2.103","article-title":"Mitochondrial Dysfunction in Parkinson\u2019s Disease","volume":"24","author":"Moon","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Choong, C.J., and Mochizuki, H. (2023). Involvement of Mitochondria in Parkinson\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242317027"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Scorziello, A., Sirabella, R., Sisalli, M.J., Tufano, M., Giaccio, L., D\u2019Apolito, E., Castellano, L., and Annunziato, L. (2024). Mitochondrial Dysfunction in Parkinson\u2019s Disease: A Contribution to Cognitive Impairment?. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111490"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1007\/s12035-020-02200-0","article-title":"Mitochondrial Protein Import Dysfunction in Pathogenesis of Neurodegenerative Diseases","volume":"58","author":"Goyal","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0925-4439(95)00038-6","article-title":"Role of mitochondria in the etiology and pathogenesis of Parkinson\u2019s disease","volume":"1271","author":"Mizuno","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/cns.13116","article-title":"Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure","volume":"25","author":"Wang","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"167992","DOI":"10.1016\/j.jmb.2023.167992","article-title":"Common Mechanisms Underlying \u03b1-Synuclein-Induced Mitochondrial Dysfunction in Parkinson\u2019s Disease","volume":"435","author":"Sohrabi","year":"2023","journal-title":"J. Mol. Biol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Jellinger, K.A., and Korczyn, A.D. (2018). Are dementia with Lewy bodies and Parkinson\u2019s disease dementia the same disease?. BMC Med., 16.","DOI":"10.1186\/s12916-018-1016-8"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1017\/S1041610208008612","article-title":"Parkinson\u2019s disease dementia and dementia with Lewy bodies: Different aspects of one entity","volume":"21","author":"Aarsland","year":"2009","journal-title":"Int. Psychogeriatr."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1212\/WNL.0000000000002001","article-title":"Longitudinal study of normal cognition in Parkinson disease","volume":"85","author":"Pigott","year":"2015","journal-title":"Neurology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s40266-022-00942-1","article-title":"Depression in Patients with Parkinson\u2019s Disease: Current Understanding of its Neurobiology and Implications for Treatment","volume":"39","author":"Prange","year":"2022","journal-title":"Drugs Aging"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1212\/CPJ.0000000000000397","article-title":"Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis","volume":"7","author":"Bock","year":"2017","journal-title":"Neurol. Clin. Pract."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Caga, J., Hsieh, S., Lillo, P., Dudley, K., and Mioshi, E. (2019). The Impact of Cognitive and Behavioral Symptoms on ALS Patients and Their Caregivers. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00192"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1007\/s00415-013-6989-9","article-title":"Behavioural and emotional symptoms of apathy are associated with distinct patterns of brain atrophy in neurodegenerative disorders","volume":"260","author":"Stanton","year":"2013","journal-title":"J. Neurol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Jellinger, K.A. (2023). The Spectrum of Cognitive Dysfunction in Amyotrophic Lateral Sclerosis: An Update. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914647"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00702-024-02850-7","article-title":"Mild cognitive impairment in amyotrophic lateral sclerosis: Current view","volume":"132","author":"Jellinger","year":"2025","journal-title":"J. Neural Transm."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1007\/s00415-021-10423-x","article-title":"Screening for cognition in amyotrophic lateral sclerosis: Test characteristics of a new screen","volume":"268","author":"Beeldman","year":"2021","journal-title":"J. Neurol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/21678421.2016.1267768","article-title":"Amyotrophic lateral sclerosis\u2014Frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria","volume":"18","author":"Strong","year":"2017","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s10072-023-07262-1","article-title":"Cognitive function in amyotrophic lateral sclerosis: A cross-sectional and prospective pragmatic clinical study with review of the literature","volume":"45","author":"Katerelos","year":"2024","journal-title":"Neurol. Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/jnnp-2015-310734","article-title":"The cognitive profile of ALS: A systematic review and meta-analysis update","volume":"87","author":"Beeldman","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1136\/jnnp-2011-300188","article-title":"The syndrome of cognitive impairment in amyotrophic lateral sclerosis: A population-based study","volume":"83","author":"Phukan","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/protein\/gzaa008","article-title":"Exposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V","volume":"32","author":"Claes","year":"2019","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pharmthera.2013.08.003","article-title":"The role of heat shock proteins in Amyotrophic Lateral Sclerosis: The therapeutic potential of Arimoclomol","volume":"141","author":"Kalmar","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Shahheydari, H., Ragagnin, A., Walker, A.K., Toth, R.P., Vidal, M., Jagaraj, C.J., Perri, E.R., Konopka, A., Sultana, J.M., and Atkin, J.D. (2017). Protein Quality Control and the Amyotrophic Lateral Sclerosis\/Frontotemporal Dementia Continuum. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00119"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainresbull.2011.10.004","article-title":"Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases","volume":"87","author":"Smith","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/ana.23937","article-title":"Stages of pTDP-43 pathology in amyotrophic lateral sclerosis","volume":"74","author":"Brettschneider","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S1474-4422(10)70195-2","article-title":"TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"9","author":"Mackenzie","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Mejzini, R., Flynn, L.L., Pitout, I.L., Fletcher, S., Wilton, S.D., and Akkari, P.A. (2019). ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now? Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01310"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Jankovic, M., Novakovic, I., Gamil Anwar Dawod, P., Gamil Anwar Dawod, A., Drinic, A., Abdel Motaleb, F.I., Ducic, S., and Nikolic, D. (2021). Current Concepts on Genetic Aspects of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189832"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ymthe.2016.10.013","article-title":"Motor-Coordinative and Cognitive Dysfunction Caused by Mutant TDP-43 Could Be Reversed by Inhibiting Its Mitochondrial Localization","volume":"25","author":"Wang","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40478-020-01111-4","article-title":"Dysfunction in nonsense-mediated decay, protein homeostasis, mitochondrial function, and brain connectivity in ALS-FUS mice with cognitive deficits","volume":"9","author":"Ho","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Kvetnoy, I., Kheyfets, O., Safaniev, L., Kheifets, V., Mironova, E., Kvetnaia, T., Mazzoccoli, G., Prashchayeu, K., and Gavrilova, A. (2025). Signaling Molecules and Diagnosis of Cognitive Disorders: Current State and Prospects. Int. J. Mol. Sci., 27.","DOI":"10.20944\/preprints202511.0968.v1"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Villa, C. (2020). Biomarkers for Alzheimer\u2019s Disease: Where Do We Stand and Where Are We Going?. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040238"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Pawlowski, M., Meuth, S.G., and Duning, T. (2017). Cerebrospinal Fluid Biomarkers in Alzheimer\u2019s Disease-From Brain Starch to Bench and Bedside. Diagnostics, 7.","DOI":"10.3390\/diagnostics7030042"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/brain\/awad267","article-title":"The potential of blood neurofilament light as a marker of neurodegeneration for Alzheimer\u2019s disease","volume":"147","author":"Jung","year":"2024","journal-title":"Brain"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1093\/brain\/awab223","article-title":"Plasma GFAP is an early marker of amyloid-\u03b2 but not tau pathology in Alzheimer\u2019s disease","volume":"144","author":"Pereira","year":"2021","journal-title":"Brain"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/acn3.51708","article-title":"Serum levels of glial fibrillary acidic protein in patients with amyotrophic lateral sclerosis","volume":"10","author":"Verde","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s11065-015-9307-8","article-title":"Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson\u2019s disease patients? A Systematic Review","volume":"25","author":"Leaver","year":"2015","journal-title":"Neuropsychol. Rev."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-019-0325-5","article-title":"Neuroimaging Biomarkers for Alzheimer\u2019s Disease","volume":"14","author":"Yassa","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.cpet.2017.02.005","article-title":"Multimodal PET Imaging of Amyloid and Tau Pathology in Alzheimer Disease and Non-Alzheimer Disease Dementias","volume":"12","author":"Xia","year":"2017","journal-title":"PET Clin."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Hessen, E. (2025). Mild cognitive impairment and neuropsychological examination. Front. Psychol., 16.","DOI":"10.3389\/fpsyg.2025.1662151"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"30835","DOI":"10.1038\/s41598-025-14062-4","article-title":"Longitudinal assessment of pragmatic and cognitive decay in healthy aging, and interplay with subjective cognitive decline and cognitive reserve","volume":"15","author":"Gabbatore","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13195-025-01921-5","article-title":"Clinical translation of fluid, imaging, and digital biomarkers for Alzheimer\u2019s disease","volume":"18","author":"Bacci","year":"2026","journal-title":"Alzheimers Res. Ther."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1016\/j.apsb.2025.07.030","article-title":"Artificial intelligence-driven multi-omics approaches in Alzheimer\u2019s disease: Progress, challenges, and future directions","volume":"15","author":"Ren","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_195","first-page":"CD005593","article-title":"Cholinesterase inhibitors for Alzheimer\u2019s disease","volume":"2006","author":"Birks","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Liu, J., Chang, L., Song, Y., Li, H., and Wu, Y. (2019). The Role of NMDA Receptors in Alzheimer\u2019s Disease. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00043"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Kruk-S\u0142omka, M., Kuce\u0142, D., Ma\u0142ysz, M., Machnikowska, A., Orzelska-G\u00f3rka, J., and Bia\u0142a, G. (2025). New Approaches to the Treatment of Alzheimer\u2019s Disease. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081117"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40262-017-0608-3","article-title":"Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer\u2019s Disease","volume":"57","author":"Hey","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/d41573-024-00180-7","article-title":"Anti-tau antibody stumbles in phase II Alzheimer trial","volume":"23","author":"Mullard","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1136\/jnnp.2006.098079","article-title":"Effect of levodopa on cognitive function in Parkinson\u2019s disease with and without dementia and dementia with Lewy bodies","volume":"77","author":"Molloy","year":"2006","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Abdelnour, C., Gibson, L.L., Batzu, L., and Aarsland, D. (2025). How to advance the pharmacological management of cognitive impairment in Parkinson\u2019s disease. J. Parkinsons Dis., 1877718x251315645.","DOI":"10.1177\/1877718X251315645"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-024-02886-y","article-title":"Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson\u2019s disease","volume":"30","author":"Pagano","year":"2024","journal-title":"Nat. Med."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00702-013-0994-0","article-title":"The practical management of cognitive impairment and psychosis in the older Parkinson\u2019s disease patient","volume":"120","author":"Hindle","year":"2013","journal-title":"J. Neural Transm."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/mds.25857","article-title":"The neurobiological basis of cognitive impairment in Parkinson\u2019s disease","volume":"29","author":"Halliday","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Duranti, E., Cordani, N., and Villa, C. (2024). Edaravone: A Novel Possible Drug for Cancer Treatment?. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031633"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/21678421.2017.1361446","article-title":"What can we learn from the edaravone development program for ALS? Amyotroph. Lateral Scler","volume":"18","author":"Maragakis","year":"2017","journal-title":"Frontotemporal Degener."},{"key":"ref_207","first-page":"61","article-title":"Riluzole: Real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis","volume":"7","author":"Hinchcliffe","year":"2017","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_208","first-page":"CD001447","article-title":"Riluzole for amyotrophic lateral sclerosis (ALS)\/motor neuron disease (MND)","volume":"2012","author":"Miller","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/17582024.2024.2402216","article-title":"Tofersen for SOD1 ALS","volume":"14","author":"Everett","year":"2024","journal-title":"Neurodegener. Dis. Manag."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"11454","DOI":"10.1021\/acs.jmedchem.2c00844","article-title":"Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy","volume":"65","author":"Fang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"116725","DOI":"10.1016\/j.ejmech.2024.116725","article-title":"PROTAC technology: From drug development to probe technology for target deconvolution","volume":"276","author":"Yan","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"117212","DOI":"10.1016\/j.ejmech.2024.117212","article-title":"Recent advances in developing targeted protein degraders","volume":"284","author":"Cheng","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"5279","DOI":"10.7150\/thno.55680","article-title":"A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejmech.2018.01.063","article-title":"Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway","volume":"146","author":"Lu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Kuemper, S., Cairns, A.G., Birchall, K., Yao, Z., and Large, J.M. (2024). Targeted protein degradation in CNS disorders: A promising route to novel therapeutics? Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1370509"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1021\/acsmedchemlett.0c00192","article-title":"PROTAC Compounds Targeting \u03b1-Synuclein Protein for Treating Neurogenerative Disorders: Alzheimer\u2019s and Parkinson\u2019s Diseases","volume":"11","author":"Kargbo","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Wen, T., Chen, J., Zhang, W., and Pang, J. (2023). Design, Synthesis and Biological Evaluation of \u03b1-Synuclein Proteolysis-Targeting Chimeras. Molecules, 28.","DOI":"10.3390\/molecules28114458"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1021\/acs.jmedchem.3c01719","article-title":"Discovery of Effective Dual PROTAC Degraders for Neurodegenerative Disease-Associated Aggregates","volume":"67","author":"Zhu","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"110449","DOI":"10.1016\/j.jbc.2025.110449","article-title":"Targeted degradation of \u03b1-synuclein by arginine-based PROTACs","volume":"301","author":"Shen","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12929-023-00921-7","article-title":"Degradation of neurodegenerative disease-associated TDP-43 aggregates and oligomers via a proteolysis-targeting chimera","volume":"30","author":"Tseng","year":"2023","journal-title":"J. Biomed. Sci."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1038\/s41467-025-60039-2","article-title":"DNA nanoflower Oligo-PROTAC for targeted degradation of FUS to treat neurodegenerative diseases","volume":"16","author":"Ge","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Behfar, Q., Richter, N., Kural, M., Clemens, A., Behfar, S.K., Folkerts, A.K., Fassbender, R., Kalbe, E., Fink, G.R., and Onur, O.A. (2023). Improved connectivity and cognition due to cognitive stimulation in Alzheimer\u2019s disease. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1140975"},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Woods, B., Aguirre, E., Spector, A.E., and Orrell, M. (2012). Cognitive stimulation to improve cognitive functioning in people with dementia. Cochrane Database Syst. Rev., CD005562.","DOI":"10.1002\/14651858.CD005562.pub2"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/mus.24202","article-title":"Rehabilitation in amyotrophic lateral sclerosis: Why it matters","volume":"50","author":"Majmudar","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1038\/s41591-025-03833-1","article-title":"Shared and disease-specific pathways in frontotemporal dementia and Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"31","author":"Ali","year":"2025","journal-title":"Nat. Med."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Gogia, N., Tare, M., Kannan, R., and Singh, A. (2023). Editorial: Protein misfolding, altered mechanisms and neurodegeneration. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1134855"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Ruffini, N., Klingenberg, S., Schweiger, S., and Gerber, S. (2020). Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. Cells, 9.","DOI":"10.20944\/preprints202010.0393.v1"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/s41593-018-0221-2","article-title":"Selective vulnerability in neurodegenerative diseases","volume":"21","author":"Fu","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"68s","DOI":"10.2967\/jnumed.121.263202","article-title":"Future Directions in Molecular Imaging of Neurodegenerative Disorders","volume":"63","author":"Barthel","year":"2022","journal-title":"J. Nucl. Med."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Maszka, P., Kwasniak-Butowska, M., Cysewski, D., Slawek, J., Smolenski, R.T., and Tomczyk, M. (2023). Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy. Metabolites, 13.","DOI":"10.3390\/metabo13030369"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"118531","DOI":"10.1016\/j.biopha.2025.118531","article-title":"Targeting protein misfolding in Alzheimer\u2019s disease: The emerging role of molecular chaperones","volume":"191","author":"Sharma","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s12035-025-05602-0","article-title":"Toward a Unified Framework in Molecular Neurobiology of Alzheimer\u2019s Disease: Revisiting the Pathophysiological Hypotheses","volume":"63","author":"Hein","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s12035-012-8324-3","article-title":"Targeting synaptic dysfunction in Alzheimer\u2019s disease therapy","volume":"46","author":"Pignatelli","year":"2012","journal-title":"Mol. Neurobiol."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/3\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T14:37:36Z","timestamp":1772548656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/3\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":233,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["neurolint18030048"],"URL":"https:\/\/doi.org\/10.3390\/neurolint18030048","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]}}}