Table 3 List of representative neurodegeneration-associated genes and cancer
From: The associations between Parkinson’s disease and cancer: the plot thickens
Gene/Protein | Biological functions | Changes in neurodegeneration | Implicated cancers |
|---|---|---|---|
SNCA/Alpha-synuclein | synaptic vesicle and dopamine release [174, 175]; excitatory transmission [176]; endoplasmic reticulum-Golgi transport [177] | major constituent of Lewy bodies; impaired neurite growth and long-term potentiation [178]; increased synaptic transmission and endoplasmic reticulum stress [177]; increased gliosis [179]; increased mitophagy [180] | adenocarcinoma, lung [181]; colorectal [182]; brain [183]; melanoma [184]; prostate [185]; non-Hodgkin lymphomas [51] |
PARK8/LRRK2 | synaptic vesicle release [186]; autophagy [187]; neurite growth and differentiation [188]; cell death signaling [189]; mitochondrial regulation [190, 191]; cytoskeletal structure maintenance [192] | increased tau phosphorylation [193]; mitochondrial and autophagic dysfunction [194]; decreased neurite outgrowth and abnormal neurogenesis [195] | |
PARK2/Parkin | synaptic transmission and dopamine release [196]; ubiquitination and protein degradation [197]; mitochondrial maintenance [198]; tumor suppressor [199] | mitophagy, mitochondrial transport and morphology defects [200]; dysfunctional UPS [60]; buildup of cyclin E and β-catenin, upregulation of Wnt and EGFR-AKT pathways [61, 73] | cervical, lung, colorectal, gastric, melanoma, endometrioid [70]; glioma [73] |
PARK6/PINK1 | serine/threonine kinase in mitochondria; mitochondrial fusion/fission regulation [201]; mitochondrial damage sensor, mitophagy and autophagic control [198]; cell cycle regulation [146]; synaptic plasticity and dopamine release [202] | increased tau phosphorylation [203]; mitochondrial dysfunction, fragmentation [204]; increased mitophagy [205]; impaired synaptic plasticity [202] | |
PARK7/DJ-1 | oxidative stress protection [208]; redox-sensitive protein chaperone [209]; transcriptional regulation, mitochondrial regulation [210–212] | increased oxidative stress sensitivity [213]; reduced complex I activity in mitochondria [214]; increased tau phosphorylation [215] | breast [216]; lung [217]; pancreatic [218]; gastric [219]; prostate [220] |
MAPT/Tau | microtubule-associated protein, tubulin polymerization, scaffolding protein [221, 222]; growth factor signaling [222]; synaptic regulation [223] | hyperphosphorylated tau, major component of neurofibrillary tangles; synapse degeneration [223] | |
APP/APP | synapse formation and maintenance [227]; trophic activity, neurite growth, axon pruning [228, 229] | mutations lead to Aβ peptide and amyloid plaques [229] |