TABLE 1.

CCT involvement in Neurological Disorders and other diseases.

Neurological diseases	CCT subunits	Mechanism of action	Citations
Alzheimer’s Disease	CCT2	Downregulated in patients	Liu et al. (2020)
Axonal transport	CCT3, CCT1 (apical)	Individual subunits normalized axonal transport and lysosomal transport	Zhao et al. (2016)
	CCT5	Regulated CDK5/p35 to increase phospho-Tau	Chen et al. (2018)
Huntington’s disease	CCT1	Single subunit reduced Htt-induced toxicity	Tam et al. (2006)
	CCT complex, CCT1	Suppressed mHtt aggregation	Tam et al. (2009)
	CCT1 (apical domain)	Inhibited aggregation of mHtt and reduced mHtt-toxicity	Sontag et al. (2013)
	CCT complex	Capped mHtt fibril tips and encapsulated smaller mHtt oligomers	Shahmoradian et al. (2013)
	CCT5	Homo-oligomer inhibited mHtt aggregation	Darrow et al. (2015)
	CCT3, CCT1 (apical)	Individual subunits reduced mHtt	Zhao et al. (2016)
Neuropathy	CCT5	Missense A492G mutation causing His147Arg described	Bouhouche et al. (2006)
	CCT5	His147Arg mutation examined in archaeal homolog	Min et al. (2014)
	CCT5	Biochemical analysis of His147Arg mutants	Sergeeva et al. (2014)
	CCT5	Structure of His147Arg mutation resolved	Pereira et al. (2017)
	CCT5	Leu224Val mutation described	Antona et al. (2020)
Parkinson’s disease	CCT2	Subunit upregulated in MPP + -treated SH-SY5Y cells	Xie et al. (2016a)
	CCT7	Oxidative stress-induced neuronal apoptosis	Anantharam et al. (2007)
	CCT complex, CCT3/6	Interfered with amyloid fibril assembly	Sot et al. (2017)
PolyQ expansion proteins	CCT complex, CCT5	Genome-wide RNA interference screen for PolyQ aggregation suppressors	Nollen et al. (2004)
	CCT complex	Synergistic function with HSP70 suppressed polyQ toxicity	Behrends et al. (2006)
	CCT complex	CCT6 knockdown and CCT1-8 overexpression modulated polyQ folding	Kitamura et al. (2006)
	CCT1	Single subunit reduced Htt-induced toxicity	Tam et al. (2006)
	CCT complex, CCT4	VRK2-mediated downregulation of CCT4 and polyQ aggregation	Kim et al. (2014)
	Targeted CCT2/5/7	Loss of function inhibited autophagy, causing protein aggregation	Pavel et al. (2016)
Protein aggregates	CCT complex, CCT4	USP25 catalyzed the de-ubiquitination of CCT reducing polyQ aggregation	Kim et al. (2015)
Other diseases	CCT Subunits	Mechanism of action	Citations
Amyotrophic lateral sclerosis	CCT5, CCT7, CCT8	Overexpressed in cytoplasm of mutant cells	Kim et al. (2017)
Primary biliary cirrhosis	CCT5	Upregulated compared to normal tissue, decreased with treatment	Chen et al. (2008)
Diabetes	CCT8	Increased in insulin-resistant vs. insulin- sensitive	Xie et al. (2016b)
	Complex, CCT8, CCT4	Increased in insulin resistance	Hwang et al. (2010)
Down syndrome	CCT5	Decreased in parietal cortex	Yoo et al. (2001)
Epilepsy	CCT1	Altered protein in hippocampi	Yang et al. (2006)
Atrial fibrillation	CCT5	Elevated protein in atrial tissue	Goudarzi et al. (2011)
Coronary artery disease	CCT6A	Upregulated gene expression based on microarray data	Balashanmugam et al. (2019)
Hepatitis C virus	CCCT complex, CCT5	Role in virus replication	Inoue et al. (2011)
Rabies virus	TCP1	Role in virus replication	Zhang et al. (2014)
Clostridium difficile Toxins	CCT4/5	Directly interacted with toxins	Steinemann et al. (2018)
Pain	CCT5	Increased expression levels in pain models	Peters et al. (2013)