{"doi":"10.3390/ijms24108593","title":"Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination","abstract":"<jats:p>The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases. Over the long course of evolution, eukaryotic cells have evolved a variety of mechanisms to rescue or eliminate aggregated proteins. Here, we will briefly review the composition and causes of protein aggregation in mammalian cells, systematically summarize the role of protein aggregates in the organisms, and further highlight some of the clearance mechanisms of protein aggregates. Finally, we will discuss potential therapeutic strategies that target protein aggregates in the treatment of aging and age-related neurodegenerative diseases.</jats:p>","journal":"International Journal of Molecular 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Li","orcid":null,"position":3,"is_corresponding":false},{"id":141427,"name":"Ji-Xin Tang","orcid":"0000-0003-0949-0547","position":4,"is_corresponding":false},{"id":141428,"name":"Hua-Feng Liu","orcid":null,"position":5,"is_corresponding":false},{"id":141423,"name":"Jun-Hao Wen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.290459441148391,"endowment":4.290459441148391,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37239937","pmcid":"PMC10217863","openalex_id":"https://openalex.org/W4378515361","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81974095","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"2019A1515110152","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"2023A1515012187","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"2022B1212030003","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"4SG21229G","title":null}],"total_grants":5,"fwci":14.0595,"citation_percentile":0.99412045,"influential_citations":1,"citation_trend":[{"year":2023,"count":4},{"year":2024,"count":30},{"year":2025,"count":31},{"year":2026,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/24/10/8593/pdf?version=1683791128","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/24/10/8593/pdf?version=1683791128","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/24/10/8593/pdf?version=1683791128","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/24/10/8593/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms24108593","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37239937","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10217863","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms24108593","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10217863/pdf/ijms-24-08593.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10217863","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10217863?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Endoplasmic Reticulum Stress and Disease","Ubiquitin and proteasome pathways","Alzheimer's disease research and treatments","Medicine","Biology","Animals","Humans","Protein Aggregates","Proteostasis","Proteostasis Deficiencies","Neurodegenerative Diseases","Proteins","Proteasome Endopeptidase Complex","Mammals"],"mesh_terms":["Proteostasis","Animals","Humans","Mammals","Proteins","Neurodegenerative Diseases","Proteasome Endopeptidase Complex","Proteostasis Deficiencies","Protein Aggregates"],"keywords":["Proteostasis","Protein aggregation","Cell biology","Biology","Protein folding","Protein degradation","Aging","Autophagy","ubiquitin-proteasome system","Protein Aggregates","Age-related Neurodegenerative 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