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Mutations, posttranslational modifications, and truncations are common molecular underpinnings in the formation of aberrant protein conformations that seed aggregation. The major proteins involved in neurodegeneration include amyloid beta (A\u03b2) and tau in Alzheimer\u2019s disease, \u03b1-synuclein in Parkinson\u2019s disease, and TAR DNA-binding protein (TDP-43) in amyotrophic lateral sclerosis (ALS). These proteins are described as intrinsically disordered and possess enhanced ability to partition into biomolecular condensates. In this review, we discuss the role of protein misfolding and aggregation in neurodegenerative diseases, specifically highlighting implications of changes to the primary\/secondary (mutations, posttranslational modifications, and truncations) and the quaternary\/supramolecular (oligomerization and condensation) structural landscapes for the four aforementioned proteins. Understanding these aggregation mechanisms provides insights into neurodegenerative diseases and their common underlying molecular pathology.<\/jats:p>","DOI":"10.3390\/ijms24043380","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T04:57:41Z","timestamp":1675832261000},"page":"3380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Aggregation of Disordered Proteins Associated with Neurodegeneration"],"prefix":"10.3390","volume":"24","author":[{"given":"Phoebe S.","family":"Tsoi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My Diem","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine C.","family":"Ferreon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8538-1732","authenticated-orcid":false,"given":"Allan Chris M.","family":"Ferreon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kovacs, G.G. 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