{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:23:39Z","timestamp":1788308619763,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NEI EY006311"],"award-info":[{"award-number":["NEI EY006311"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIA AG18031"],"award-info":[{"award-number":["NIA AG18031"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG038834"],"award-info":[{"award-number":["AG038834"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Naturally occurring neuron-abundant proteins including amyloid A\u03b242 peptide and the microtubule-associated protein tau (MAPT) can, over time and under pathological situations, assume atypical conformations, altering their normal biological structure and function, and causing them to aggregate into insoluble and neurotoxic intracellular inclusions. These misfolded proteins ultimately contribute to the pathogenesis of several progressive, age-related and ultimately lethal human neurodegenerative disorders. The molecular mechanism of this pathological phenomenon of neuronal protein misfolding lends support to the \u2018prion hypothesis\u2019, which predicts that the aberrant folding of endogenous natural protein structures into unusual pathogenic isoforms can induce the atypical folding of other similar brain-abundant proteins, underscoring the age-related, progressive nature and potential transmissible and spreading capabilities of the aberrant protein isoforms that drive these invariably fatal neurological syndromes. The abnormal folding and aggregation of host proteins is a consistent feature of both amyloidopathies and tauopathies that encompass a continuous spectrum of brain diseases that include Alzheimer\u2019s disease (AD), prion disorders (PrD) such as scrapie in sheep and goats (Bovidae), experimental prion infection of rodents (Muridae), Creutzfeldt\u2013Jakob disease (CJD) and Gerstmann\u2013Str\u00e4ussler\u2013Scheinker syndrome (GSS) in humans (Hominidae), and other fatal prion-driven neurological disorders. Because AD patients accumulate both misfolded tau and A\u03b2 peptides, AD may be somewhat unique as the first example of a \u2018double prion disorder\u2019. This commentary will examine current research trends in this fascinating research area, with a special emphasis on AD and PrD, and the novel pathological misfolded protein processes common to both intractable neurological disorders.<\/jats:p>","DOI":"10.3390\/biom12020166","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T22:40:20Z","timestamp":1642718420000},"page":"166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Recent Advances in Our Molecular and Mechanistic Understanding of Misfolded Cellular Proteins in Alzheimer\u2019s Disease (AD) and Prion Disease (PrD)"],"prefix":"10.3390","volume":"12","author":[{"given":"Walter J.","family":"Lukiw","sequence":"first","affiliation":[{"name":"Departments of Neurology, Neuroscience and Ophthalmology, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2011.10.002","article-title":"Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes","volume":"147","author":"Ingolia","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e01257","DOI":"10.7554\/eLife.01257","article-title":"Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments","volume":"3","author":"Lareau","year":"2014","journal-title":"Elife"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-1-0716-1851-6_5","article-title":"Exploring ribosome-positioning on translating transcripts with ribosome profiling","volume":"2404","author":"Cope","year":"2022","journal-title":"Methods Mol. 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