Table 1. Genetic determinants at the interface of cancer and neurodegeneration.

Gene	Function	Role in Neurodegeneration	Role in Cancer
α-synuclein (PARK1/4)	Unclear	Gain of function leads to PD [104]. Main component of Lewy bodies in PD [105].	α-synuclein is aberrantly expressed and methylated in cancer [106].
PINK1 (PARK6)	Kinase	Loss of function leads to PD [50]. Loss of PINK1 functions leads to mitochondrial deficits.	Somatic mutations in cancer (COSMIC Web site). Tumour suppressor? Induced by PTEN [92].
DJ-1 (PARK7)	Unclear	Loss of function leads to PD [87]. DJ-1 might act as a neuroprotective oxidative stress sensor.	Oncogene [86]. Regulates negatively PTEN. Over-expression in several tumours.
LRRK2 (PARK8)	Kinase, GTPase	Gain of function leads to PD [51], [52]. Enzymatic activities thought to play key role in disease [105].	Somatic mutations in cancer (COSMIC Web site). Oncogene?
ATP13A2 (PARK9)	ATPase	Loss of function leads to PD [107]. May alter autophagic lysosomal function.	ALP plays an important role in cancer.
PLA2G6 (PARK14?)	Phospholipase A2	Mutations lead to infantile neuroaxonal dystrophy (INAD), idiopathic neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism [71].	PLA2G6 was identified as a risk factor for melanoma [69].
Tau (MAPT)	Microtubule-associated protein	Mutations in Tau lead to AD and FTDP-17 [105], [108] Tau is the major component of neurofibrillary tangles in AD.	Reduced expression in several tumours.
APP/PS1,2	Unclear	Gain of function leads to AD type [109]. Mutations in APP and the presenilins increases production of Aβ, which is the main component of senile plaques in AD.	APP is overexpressed in acute myeloid leukemia patients with complex karyotypes [110].
SOD1	Superoxide dismutase	Gain of function leads to ALS. Mutations thought to cause cell death via aggregation and oxidative damage [111], [112].	Role in breast cancer? [113]
Huntingtin	Unclear	Gain of function leads to HD [114].
Parkin (PARK2)	E3 ubiquitin ligase	Loss of function leads to PD [40]. Parkin enzymatic activity is thought to play a key role in disease. Loss of parkin function leads to mitochondrial deficits [115], [116].	Tumour suppressor [46].
ATM	Kinase (PI3K)	Mutations in the ATM gene cause ataxia-telangiectasia [30]. ATM inactivation leads to cerebellar neuron loss.	Tumour suppressor. ATM mutations carriers at increased risk of developing cancer, especially breast cancer. Role in cell cycle and DNA damage.
CDK5	Kinase	CDK5 can phosphorylate Tau [117] and parkin [118]. Also is associated with AD [95].	Somatic mutations in cancer.
p53	Transcription factor	Functional link between p53 and parkin, Ab and APP [83].	Tumour suppressor [33].
PTEN	Phosphatase	Functional link between PTEN and PINK1, parkin and DJ-1 [119].	Tumour suppressor, mutated in sporadic and inherited tumours [120].
mTOR	Kinase	May play a role in neurodegeneration through inhibition of autophagy.	Autophagy can be both oncogenic as well as tumour suppressive.
TSC1/TSC2	Vesicular transport	May play a role in neurodegeneration through mTOR-dependant autophagy.	Tumour suppressors [121].

Common factors and overlapping pathways can be identified in the progression of both cancer and neurodegeneration. A number of molecules genetically associated with these diseases are kinases and/or play a role in apoptosis, cell cycle, and DNA repair. Protein degradation pathways are often disturbed in both cancer and neurodegeneration. Mitochondrial dysfunction and oxidative stress are also shown to cause both diseases. Finally, the autophagic lysosomal pathway is increasingly recognised as playing a major role in the physiopathological mechanisms associated with both the disorders. Importantly, all these processes are regulated during aging, the first risk factor for both cancer and neurodegeneration.

In bold—Strong genetic association with neurodegeneration.

In italic—Strong genetic association with cancer.

In bold and in italic—Strong genetic association with both cancer and neurodegeneration.