PARK9 Antibody #5879

Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s, is a progressive movement disorder characterized by rigidity, tremors and postural instability. The pathological hallmark of PD is progressive loss of dopaminergic neurons in the substantia nigra of the ventral midbrain and the presence of intracellular Lewy bodies (protein aggregates of α-synuclein, ubiquitin and other components) in surviving neurons of the brain stem (1). Various genes and loci (α-synuclein/PARK1 and 4, parkin/PARK2, UCH-L1/PARK5, PINK1/PARK6, DJ-1/PARK7, LRRK2/PARK8, ATP13A2/PARK9) are genetically linked to PD (2).

PARK9, also known as ATP13A2, is a member of the P-type ATPase superfamily and is involved in the lysosomal degradation pathway, clearing α-synuclein aggregates (3,4). The protein has 10 transmembrane domains and wild-type PARK9 localizes to the lysosomal membrane. In contrast, all three known mutations, which have premature stop codons resulting in a truncated protein, are retained in the endoplasmic reticulum and degraded by the proteasome. PARK9 is predominantly expressed in the brain and has been linked to Kufor-Rakeb Syndrome, a monogenic form of recessively inherited, atypical parkinsonism that is characterized by juvenile-onset, with pyramidal degeneration and cognitive dysfunction (4,5).