Neuropathology and defects in COG-associated proteins
Extensive in vitro analyses in control and disease models demonstrate that genetic deficiency in SNARE and Rab COG partners may also result in disintegration of the Golgi apparatus, thereby potentially influencing neurological impairment (Table 1). Interestingly, the therapeutic implications of studying neurodegeneration associated with defective COG function is broader than the COG-CDG patient population (D'Adamo et al., 2014; Rymen et al., 2015). Golgi fragmentation is a common feature of neurodegenerative diseases (Gonatas et al., 2006). Current theories argue that the Golgi fragmentation seen in Alzheimer's Disease (AD) and Parkinson's Disease (PD) is either a result of misfolded or aggregated proteins, or that fragmented Golgi causes etiologically important proteins to aggregate and misfold leading to further progression of these diseases (Gonatas et al., 2006; Nakagomi et al., 2008; Bellouze et al., 2014; Joshi and Wang, 2015). However, Golgi fragmentation has also been linked to SNARE and Rab proteins making it difficult to pinpoint a single disease progression. Thus, the COG-Rab-SNARE dynamic is important for understanding neurodegenerative phenotypes.