{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:12:29Z","timestamp":1791886349346,"version":"4.3.4"},"reference-count":269,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A6A1A03025124"],"award-info":[{"award-number":["NRF-2018R1A6A1A03025124"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial\u2013endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-\u03b2 (A\u03b2) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/cells14151179","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T06:37:47Z","timestamp":1754030267000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chaperone-Mediated Responses and Mitochondrial\u2013Endoplasmic Reticulum Coupling: Emerging Insight into Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-0350","authenticated-orcid":false,"given":"Manish Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8176-3672","authenticated-orcid":false,"given":"Minghao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotsna S.","family":"Ranbhise","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-9482","authenticated-orcid":false,"given":"Wonchae","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-7668","authenticated-orcid":false,"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-1008","authenticated-orcid":false,"given":"Insug","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0140-6736(10)61349-9","article-title":"Alzheimer\u2019s disease","volume":"377","author":"Ballard","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1017\/S1041610223000431","article-title":"Rarer dementias, limited options, and unaddressed needs: Commentary on \u201cA Mixed Methods Evaluation of a Programme Exploring Pre-death Grief and Loss for Carers of People with Rarer Dementias,\u201d by Stevens-Neck et al","volume":"36","author":"Cummings","year":"2024","journal-title":"Int. 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