INVESTIGATION OF THE SYNERGIC EFFECT OF β-SYNUCLEIN WITH HSP27 ON NEUROPROTECTION

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TWO MISSENSE MUTATIONS (P123H AND V70M) OF BETA-SYNUCLEIN, THE HOMOLOGUE OF ALPHA-SYNUCLEIN, HAVE BEEN RECENTLY IDENTIFIED IN DEMENTIA WITH LEWY BODIES, HOWEVER, THE MECHANISM THROUGH WHICH THESE MUTATIONS INFLUENCE THE PATHOGENESIS OF DEMENTIA WITH LEWY BODIES IS UNCLEAR, TO INVESTIGATE THE ROLE OF THE BETA-SYNUCLEIN MUTATIONS IN NEURODEGENERATION, EACH MUTANT WAS STABLY TRANSFECTED INTO B103 NEUROBLASTOMA CELLS CELLS OVEREXPRESSING MUTATED BETA-SYNUCLEIN HAD ENHANCED LYSOSOMAL, ACTIVITY AND LYSOSOMAL INCLUSION BODIES IN THE CYTOPLASM, SUGGESTING THAT THESE MISSENSE MUTATIONS OF BETA_SYNUCLEIN MIGHT PLAY A CAUSATIVE ROLE IN STIMULATING NEURODEGENETION. SUBSEQUENTLY, WE CREATED TRANSGENIC MICE OVEREXPRESSING P123H BETA-SYNUCLEIN USING THY-1 PROMOTER. THE MICE EXHIBITED AXONAL DEGENERATION AND SYNAPTIC TERMINAL SWELLING, ASSOCIATED WITH PROTEIN AGGREGATION AND BEHAVIOURAL ABNORMALITIES, INCLUDING MOTER DYSFUNCTION. THUS, THESE TRANSGENIC MICE MAY BE USEFUL AS NEW SYNUCLEINOPATHY MODEL MICE. FURTHER STUDY IS IN PROGRESS, INCLUDING CREATION OF BIGENIC MICE BETWEEN P123H BETA-SYNUCLEIN TRANSGENIC MICE AND ALPHA-SYNUCLEIN TRANSGENIC MICE.