{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:25:35Z","timestamp":1792041935358,"version":"4.4.0"},"reference-count":281,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273107"],"award-info":[{"award-number":["82273107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472721"],"award-info":[{"award-number":["82472721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470571"],"award-info":[{"award-number":["32470571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative diseases are the leading cause of human disability and immensely reduce patients\u2019 life span and quality. The diseases are characterized by the functional loss of neuronal cells and share several common pathogenic mechanisms involving the malfunction, structural distortion, or aggregation of multiple key regulatory proteins. Cellular phase separation is the formation of biomolecular condensates that regulate numerous biological processes, including neuronal development and synaptic signaling transduction. Aberrant phase separation may cause protein aggregation that is a general phenomenon in the neuronal cells of patients suffering neurodegenerative diseases. In this review, we summarize the pathological causes of common neurodegenerative diseases, including Alzheimer\u2019s disease, Parkinson\u2019s disease, and Huntington\u2019s disease, among others. We discuss the regulation of key amyloidogenic proteins with an emphasis of their aberrant phase separation and aggregation. We also introduce the approaches as potential therapeutic strategies to ameliorate neurodegenerative diseases through intervening protein aggregation. Overall, this review consolidates the research findings of phase separation and aggregation caused by misfolded proteins in a context of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms251810187","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:36:38Z","timestamp":1727062598000},"page":"10187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3677-1392","authenticated-orcid":false,"given":"Yinuo","family":"Wu","sequence":"first","affiliation":[{"name":"Aulin College, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0500-2821","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dangdang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-5585","authenticated-orcid":false,"given":"Guangchao","family":"Sui","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref_1","unstructured":"GBD Nervous System Disorders Collaborators (2024). 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