Abstract
Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer.
Highlights
Parkinson’s disease (PD) is a progressive, age-related neurodegenerative disorder, primarily defined by its related movement disabilities, including resting tremor, muscle tone rigidity and bradykinesia [1]
We tested whether Alpha Synuclein (a-Syn), a neuronal protein implicated in neuronal loss in PD and the related synucleinopathies, is involved in mechanisms of peripheral tumor growth and proliferation
We tested the involvement of a-Syn expression in the growth and proliferation of murine B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma
Summary
PD is a progressive, age-related neurodegenerative disorder, primarily defined by its related movement disabilities, including resting tremor, muscle tone rigidity and bradykinesia [1]. PD is characterized by dopaminergic neuronal loss in the nigro-striatal pathway of the brain and by the presence of Lewy bodies and Lewy neurites (reviewed in [3]) that with disease progression, spreads from the brain stem to the frontal neocortex [4]. A progressive conversion of the soluble a-Syn protein, into soluble oligomers and insoluble aggregates is preceding its intraneuronal cytoplasmic deposition and underlies its cytopathology in this group of disorders [9,10]. This progressive conversion and accumulation in cytotoxic forms of a-Syn is associated with neurodegeneration in PD [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
