{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:27:25Z","timestamp":1791502045398,"version":"4.3.4"},"reference-count":181,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein damage, thus exacerbating protein misfolding and leading to an eventual overload of the degradation system. The regulation of proteostasis network is particularly important in postmitotic neurons due to their limited regenerative capacity. Therefore, maintaining balanced protein synthesis, handling unfolding, refolding, and degrading misfolded proteins are essential to preserve all cellular functions in the central nervous sysytem. Failing proteostasis may trigger inflammatory responses in glial cells, and the consequent release of inflammatory mediators may lead to disturbances in proteostasis. Here, we review the mechanisms of proteostasis and inflammatory response, emphasizing their role in the pathological hallmarks of neurodegenerative diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis. Furthermore, we discuss the interplay between proteostatic stress and excessive immune response that activates inflammation and leads to dysfunctional proteostasis.<\/jats:p>","DOI":"10.3390\/cells9102183","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T08:02:58Z","timestamp":1601280178000},"page":"2183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"9","author":[{"given":"Tuuli-Maria","family":"Sonninen","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Neulaniementie 2, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundars","family":"Goldsteins","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Neulaniementie 2, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8718-4612","authenticated-orcid":false,"given":"Nihay","family":"Laham-Karam","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Neulaniementie 2, 70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Neulaniementie 2, 70211 Kuopio, Finland"},{"name":"Neuroscience Center, University of Helsinki, Haartmaninkatu 8, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-9414","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Neulaniementie 2, 70211 Kuopio, Finland"},{"name":"Neuroscience Center, University of Helsinki, Haartmaninkatu 8, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte barriers to neurotoxic inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nrn3722","article-title":"Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease","volume":"15","author":"Prinz","year":"2014","journal-title":"Nat. Rev. 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