{"doi":"10.3390/ijms26041525","title":"Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles","abstract":"<jats:p>Protein misfolding, aggregation, and aberrant aggregate accumulation play a central role in neurodegenerative disease progression. The proteotoxic factors also govern the aging process to a large extent. Molecular chaperones modulate proteostasis and thereby impact aberrant-protein-induced proteotoxicity. These chaperones have a diverse functional spectrum, including nascent protein folding, misfolded protein sequestration, refolding, or degradation. Small heat shock proteins (sHsps) possess an ATP-independent chaperone-like activity that prevents protein aggregation by keeping target proteins in a folding-competent state to be refolded by ATP-dependent chaperones. Due to their near-universal upregulation and presence in sites of proteotoxic stress like diseased brains, sHsps were considered pathological. However, gene knockdown and overexpression studies have established their protective functions. This review provides an updated overview of the sHsp role in protein aggregation amelioration and highlights evidence for sHsp modulation of neurodegenerative disease-related protein aggregation and aging.</jats:p>","journal":"International Journal of Molecular Sciences","year":2025,"id":35536,"datarank":0.46901982933792785,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.08427742571869727,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.08427742571869727,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":11,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":181797,"name":"Bothina Mohammed Alharbi","orcid":null,"position":1,"is_corresponding":false},{"id":181798,"name":"Entissar S. AlSuhaibani","orcid":null,"position":2,"is_corresponding":false},{"id":181799,"name":"Sameer Mohammad","orcid":"0000-0002-1129-7685","position":3,"is_corresponding":false},{"id":181800,"name":"Shuja Shafi Malik","orcid":"0000-0003-3496-2112","position":4,"is_corresponding":false},{"id":181795,"name":"Tahani H. Albinhassan","orcid":"0000-0002-2487-8286","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40003991","pmcid":"PMC11855743","openalex_id":"https://openalex.org/W4407364089","authors":[],"funders":[{"funder_name":"King Abdullah International Medical Research Center","grant_id":"NRC23R/596/09","title":null}],"total_grants":1,"fwci":6.4058,"citation_percentile":0.96831984,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/26/4/1525/pdf?version=1739291064","host_type":"journal"},{"url":"https://doi.org/10.3390/ijms26041525","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/26/4/1525/pdf?version=1739291064","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/26/4/1525/pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40003991","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11855743","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11855743/pdf/ijms-26-01525.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11855743","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11855743?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Heat shock proteins research","Endoplasmic Reticulum Stress and Disease","Enzyme Structure and Function","Medicine","Biology","Humans","Heat-Shock Proteins, Small","Aging","Protein Aggregates","Animals","Neurodegenerative Diseases","Protein Aggregation, Pathological","Proteostasis","Protein Folding","Molecular Chaperones"],"mesh_terms":["Proteostasis","Aging","Animals","Humans","Protein Folding","Molecular Chaperones","Neurodegenerative Diseases","Heat-Shock Proteins, Small","Protein Aggregation, Pathological","Protein Aggregates"],"keywords":["Proteostasis","Proteotoxicity","Protein aggregation","Protein folding","Heat shock protein","Chaperone (clinical)","Aggresome","Cell biology","HSF1","Biology","CLPB","Chemical chaperone","Unfolded protein response","Chemistry","Hsp70","Biochemistry","Ubiquitin","Gene","Endoplasmic reticulum","Medicine","Aging","Proteome","Neurodegenerative Disorders","Amyloid Fibrils","Small Heat Shock Proteins","Protein-folding"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T04:33:30.189200Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}