Table 3.
Genes/proteins involved in PD
| Gene symbol | Gene/protein name | Protein function | Reference | Sporadic (s) / familial (f) | Notes |
|---|---|---|---|---|---|
| ATP13A2 | ATPase cation transporter 13A2 | lysosomal transmembrane protein associated with inorganic cations transport | 121 | f | Mutations produce truncated inactive proteins and cause an atypical form of PD (Kufor-Rakeb syndrome), with juvenile onset and rapid progression. Recessive inhheritance. |
| DJ-1 | DJ-1 | Molecular chaperone which acts as cellular sensor of oxidative stress and protecits mitochondria | 122 | f | Earky onset and slow disease progression. Recessive inhheritance. |
| GBA1 | Beta-glucosylceramidase—glucocerebrosidase | lysosomal enzyme involved in glycolipid metabolism | 123,124 | s | Heterozygous mutations cause accumulation of glucocerebroside in different organs and are considered the greatest genetic risk factor for PD also associated with reduced age of onset. |
| LRRK2 | Leucine-rich repeat kinase 2 | neurite and synapse formation, membrane trafficking, autophagy | 125 | s/f | Missense mutations result in amino acid substitutions that increase protein activity. Mutations in the LRKK2 gene are the most common cause of inheritable and sporadic PD, with mid-to-late onset and slow progression. Dominant inheritance. |
| PINK1 (PARK6) | PTEN-induced putative kinase | serine-threonine mitochondrial kinase involved in mitochondrial function together with parkin | 126 | f | Truncating, missense and nonsense point and frameshift mutations result in dysfunctional protein; early onset. Recessive inhheritance. |
| PRKN | Parkin | E3 ubiquitin ligase regulating mitochondrial function and protein quality control system | 127 | s/f | It is the most common cause of autosomal recessive PD, with early onset (less than 40 years old) and slow progression. Recessive inheritance |
| SNCA | α-synuclein | synaptic function and neurotransmission | 128 | s (rarely)/f | Amino acid substitutions, due to missense mutations or increased protein expression, due to gene locus multiplications, render α-syn prone to aggregation. Dominant inheritance. |
Abbreviation: PD, Parkinson’s disease.