Table 1.
Genes involved in Parkinson’s disease pathogenesis, function, phenotype, and neuropathology
| Gene | Gene function | Phenotype | Results of gene mutation |
|---|---|---|---|
| SNCA | α-synuclein protein is the product of the SNCA gene that abundantly spreads in neurons; its function is not yet fully understood but it may play role in the control of vesicular neurotransmission as well as dopamine neurotransmission | Early-onset PD | Widespread presence of LB in the cerebral cortex and brainstem, neuronal degeneration in the SN and LC |
| PARKIN | Parkin is an E3 ubiquitin ligase which plays role in proteasome-dependent degradation of proteins. It destroys misfolded and excess proteins with ubiquitin | Early-onset PD | Absence of LB, apoptosis of dopaminergic neurons from the SN, and neurofibrillary tangle pathology in the brainstem and cerebral cortex |
| PINK1 | The PINK1 gene produces a protein called PTEN-induced putative kinase 1. This protein functions in the mitochondria protect the mitochondria from destructive effects of cellular oxidative stress | Early-onset PD | Neuronal loss in the SN pars compacta and presence of LB in the reticular nuclei of the brainstem |
| LRRK2 | The product of LRRK2 gene belongs to the Roco protein family. It plays roles in autophagy, cytoskeletal dynamics, and vesicular transport | Classical PD | Heterogeneous: loss of neurons in the SN and presence of LB in the brainstem and; Some cases: absence of LB and neuronal nigral loss, neurofibrillary tangle pathology |
| D-J1 | DJ-1 protein is found in many organs and tissues, such as the brain. This protein appears to have protected cells from oxidative stress and also serves as a chaperone molecule. DJ-1 supports the folding of newly proteins into the proper three-dimensional shape and the refolding of damaged ones | Early-onset PD | LB pathology |
| RAB39B | RAB proteins, such as RAB39B, are belonged to GTPases family. RAB39B regulates vesicular trafficking between membrane compartments | X-linked early-onset PD | Widespread dopaminergic neuronal loss in the SN and classic LB disease |
PD Parkinson’s disease, LB Lewy body, LC locus coeruleus, SN substantia nigra