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Cognitive impairment is a common phenotype of DS and Alzheimer\u2019s disease (AD), and overexpression of <jats:italic>TTC3<\/jats:italic> can accelerate cognitive decline, but the specific mechanism is unknown. The TTC3-mediated protein quality control (PQC) mechanism, similar to the PQC system, is divided into three parts: it acts as a cochaperone to assist proteins in folding correctly; it acts as an E3 ubiquitin ligase (E3s) involved in protein degradation processes through the ubiquitin\u2013proteasome system (UPS); and it may also eventually cause autophagy by affecting mitochondrial function. Thus, this article reviews the research progress on the structure, function, and metabolism of TTC3, including the recent research progress on TTC3 in DS and AD; the role of TTC3 in cognitive impairment through PQC in combination with the abovementioned attributes of TTC3; and the potential targets of TTC3 in the treatment of such diseases.<\/jats:p>","DOI":"10.1007\/s10571-021-01060-z","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T08:02:25Z","timestamp":1614412945000},"page":"1659-1669","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment"],"prefix":"10.1007","volume":"42","author":[{"given":"Xu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongjin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-2531","authenticated-orcid":false,"given":"Lili","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"1060_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s12192-010-0248-0","volume":"16","author":"RK Allan","year":"2011","unstructured":"Allan RK, Ratajczak T (2011) Versatile TPR domains accommodate different modes of target protein recognition and function. 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