Next to SNCA, the expression of several other genes known as genetic risk factors for PD7,8 were related to the Braak staging scheme. Two genes ZNF184 (zinc finger protein 184) and ELOVL7 (fatty acid elongase 7) have recently been associated with early onset PD in a Chinese population29. SCARB2 (scavenger receptor class B member 2) encodes for the lysosomal integral membrane protein-2 (LIMP2), the specific receptor for glucocerebrosidase (GCase), and is important for transport of GCase from the endoplasmic reticulum via Golgi to lysosomes30. SCARB2-deficiency in mice brains led to α-synuclein accumulation mediating neurotoxicity in dopaminergic neurons30. Overexpression in murine and human cell lines improved lysosomal activity of this enzyme and enhanced α-synuclein clearance30. SH3GL2 (SH3 Domain Containing GRB2 Like 2, Endophilin A1) is thought to act downstream of LRRK2 to induce synaptic autophagosome formation and may be deregulated in PD31. BAP1 (ubiquitin carboxyl-terminal hydrolase) is a deubiquitinase that acts as a tumor suppressor. Cancer-associated mutations within this gene were found to destabilize protein structure promoting amyloid-β aggregation in vitro, which is the pathological hallmark in Alzheimer’s disease32.
