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Novel AlphasynucleinPAN in Human Mesenchymal Stem Cells-Derived Neurons Masks SNCA140 and Creates Dissociation of deleterious SNCA98 in Astrocytoma Stem Cells

Akeem G Owoola, Rachel K. Okolicsanyi, Lyn R. Griffiths, Larisa M. Haupt

Alzheimer’s Dementia (AD) and Parkinson’s disease Dementia (PDD) are common causes of dementia characterised by misfolded alpha-Synuclein (SNCA) proteins, amyloid precursor proteins (APP), and Microtubule Associated Protein Tau (MAPT). Accumulation of alpha synuclein is involved in cancer. SNCA140 increases oxidative stress, and this leads to elevated amyloidogenic APP processing. There is currently no effective/disease modifying treatment of AD and PDD. Human Mesenchymal Stem Cells (HMSCs) are promising therapeutic candidates for the repair and regeneration of neural cells, but their viable clinical application in AD and PDD treatment requires consideration of epistatic influence of the lineage substitution of SNCA.

Objectives: Here, we hypothesised that SNCAPAN exhibit lineage substitution in hMSCs-derived neurons, and it is epistatic to SNCA140 expression.

Methodology: We examined phenotypic characteristic of AD and PDD biomarkers in hMSCs-derived neurons at p+6 in four biological replicates (n=4) with non-template controls (NTCs, n=2) for each target gene using a Q-PCR. Amplification reactions in NTCSNCA98 and NTCSNCA115 were validated by gel electrophoresis. SNCA98-SNCA126 molecular interaction observed was determined using spearman’s rank correlation regression, and this was validated by gel electrophoresis of generic PCR (50^°C, 52^°C, 54^°C, 56^°C, 58^°C, and 60^°C) with NTC using Universal human reference RNA (UHRR) and astrocytoma stem cells. Expression of each gene was normalised to 18S, the endogenous control. Data are presented as mean 2(-ΔΔCt) ± SEM.

Results: SNCAPAN exhibits lineage substitution in hMSC-derived neurons, and it is epistatic to SNCA140 expression, a first time viable novel structural remodelling functional innovation in the treatment of AD, PDD, and Brain Cancer. In SNCA98 and SNCA115, there were NTC amplification reactions. SNCA98 and SNCA115 expressions are significantly higher compared to APP (P=0.002947735; P=1.3411E-07), MAPT (P=0.00184993; P=5.15474E-05), SNCAPAN (P=0.003579771; P=3.69932E-06), SNCA112 (P=0.006057562; P=9.06788E-05), and SNCA126 (P=0.001054018; P=2.36E-05) respectively. SNCA98 expression extremely and significantly correlates with SNCA126 expression (ρ=0.9827; P=3.71669E-05).

Conclusion: The UHRR of gel electrophoresis of generic PCR containing SNCA126 in astrocytoma stem cells at 50^°C and 52^°C confirms the significant SNCA98-SNCA126 relationship as sign epistasis (deleterious SNCA98 enhances beneficial SNCA126) due to synergistic epistatic background created by SNCAPAN, and this validates the epistasis of SNCAPAN to SNCA140.