{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:47:21Z","timestamp":1790999241693,"version":"4.1.0"},"reference-count":165,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02843"],"award-info":[{"award-number":["2018-02843"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer Foundation","award":["AF940014"],"award-info":[{"award-number":["AF940014"]}]},{"DOI":"10.13039\/501100000942","name":"Brain Foundation","doi-asserted-by":"publisher","award":["Fo 2019-0140"],"award-info":[{"award-number":["Fo 2019-0140"]}],"id":[{"id":"10.13039\/501100000942","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation for Geriatric Diseases at Karolinska Institutet","award":["2021-00681"],"award-info":[{"award-number":["2021-00681"]}]},{"name":"Gunvor and Josef An\u00e9rs Foundation"},{"DOI":"10.13039\/100009673","name":"Gun and Bertil Stohnes Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009673","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tore Nilssons Foundation for medical research"},{"name":"Mar-garetha af Ugglas Foundation"},{"name":"the Foundation for Old Servants","award":["2020-01028"],"award-info":[{"award-number":["2020-01028"]}]},{"name":"Magnus Bergvalls Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The dysfunction of the proteostasis network is a molecular hallmark of neurodegenerative diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease, and amyotrophic lateral sclerosis. Molecular chaperones are a major component of the proteostasis network and maintain cellular homeostasis by folding client proteins, assisting with intracellular transport, and interfering with protein aggregation or degradation. Heat shock protein 70 kDa (Hsp70) and 90 kDa (Hsp90) are two of the most important chaperones whose functions are dependent on ATP hydrolysis and collaboration with their co-chaperones. Numerous studies implicate Hsp70, Hsp90, and their co-chaperones in neurodegenerative diseases. Targeting the specific protein\u2013protein interactions between chaperones and their particular partner co-chaperones with small molecules provides an opportunity to specifically modulate Hsp70 or Hsp90 function for neurodegenerative diseases. Here, we review the roles of co-chaperones in Hsp70 or Hsp90 chaperone cycles, the impacts of co-chaperones in neurodegenerative diseases, and the development of small molecules modulating chaperone\/co-chaperone interactions. We also provide a future perspective of drug development targeting chaperone\/co-chaperone interactions for neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/cells10102596","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T08:27:44Z","timestamp":1632904064000},"page":"2596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Targeting Chaperone\/Co-Chaperone Interactions with Small Molecules: A Novel Approach to Tackle Neurodegenerative Diseases"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6482-1073","authenticated-orcid":false,"given":"Lisha","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neuroscience Care and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Bergkvist","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Care and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Care and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164 Solna, Sweden"},{"name":"Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi 221005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Winblad","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Care and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164 Solna, Sweden"},{"name":"Theme Inflammation and Aging, Karolinska University Hospital, 14186 Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-5654","authenticated-orcid":false,"given":"Pavel F.","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Care and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1126\/science.1141448","article-title":"Adapting proteostasis for disease intervention","volume":"319","author":"Balch","year":"2008","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-biochem-060614-033955","article-title":"The biology of proteostasis in aging and disease","volume":"84","author":"Labbadia","year":"2015","journal-title":"Annu. 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