Table 3.

Neuropathology and defects in COG-associated proteins

COG partners
ATP7A	Menkes disease	Early childhood neurodegeneration, severe neurologic impairment	Zlatic et al. (2015)
GM130	Neurodegeneration	Developmental delay, ataxia, decreased size of dendritic arbors	Liu et al. (2017) and Zhou et al. (2014)
GS27	Myoclonus epilepsy/early ataxia Parkinson’s disease	Lack muscle coordination, gait abnormality. Trafficking deficient cytotoxicity in NRK and PC12 cells	Corbett et al. (2011) and Thayanidhi et al. (2010)
GS28	Neurodegeneration	Retinal degeneration in D. melanogaster photoreceptors	Rosenbaum et al. (2014)
Rab1a	Parkinson’s disease sporadic ALS	Neuroprotective in C. elegans, D. melanogaster, and rat neurons, rescue from the neurotoxic effects of α-Syn. Rab1 is misfolded and dysfunctional resulting in defective ER-Golgi trafficking	Cooper et al. (2006), Gitler et al. (2008), and Soo et al. (2015)
Rab1b	Alzheimer’s disease	Dominant negative Rab1b blocks trafficking of APP and decreased the secretion of Ab	Dugan et al. (1995)
Rab2	Parkinson’s disease	Reduced expression of Rab2 rescues Golgi fragmentation in PD models	Rendon et al. (2013)
Rab4a	Neumann-Pick disease, Alzheimer’s disease, Down syndrome	Developmental delays and dementia. Postmortem samples: Increased Rab4 in patients with AD and mild cognitive disorder. Aβ partially co-localizes with Rab4 in a mouse model of Down Syndrome	Arriagada et al. (2010), Cataldo et al. (2000), Choudhury et al. (2004), and Ginsberg et al. (2010)
Rab6a	Alzheimer’s disease	Dominant negative mutant of Rab6 increased the secretion of sAPP and decreased Aβ secretion	McConlogue et al. (1996)
Sec22b	Parkinson’s disease	Trafficking-deficient cytotoxicity in NRK and PC12 cells	Hasegawa et al. (2003, 2004)
SNAP29	CEDNIK syndrome	Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma	Sprecher et al. (2005) and Fuchs-Telem et al. (2011)
STX5	Parkinson’s disease, neurodegeneration, Alzheimer’s disease	Trafficking-deficient cytotoxicity in NRK and PC12 cells. Decreased STX5 causes accumulation and degradation of rhodopsin in D. melanogaster photoreceptors. Regulates processing of APP in PC12, HeLa, COS-7, and NG108–15 cell lines and hippocampal neurons, overexpressed STX5 coincides with accumulation of Aβ	Rendon et al. (2013), Thayanidhi et al. (2010), Satoh et al. (2016), and Suga et al. (2005, 2015)
Vti1a/b	Neurodegeneration	Perinatal lethality in double knockouts mouse model. Neurodegenerative phenotypes: Major axon tracks are missing, reduced in size, or misrouted	Kunwar et al. (2011) and Walter et al. (2014)
Ykt6	Parkinson’s disease	Trafficking deficient cytotoxicity in NRK and PC12 cells	Hasegawa et al. (2003, 2004)