Parkinson’s disease (PD) is the most secondary neurodegenerative disease in the world. The most obvious symptoms in clinic are movement-related, which companies a selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of intraneuronal Lewy bodies (LBs) in pathology. Alpha-synuclein (α-syn) as a major structural component in LBs was considered closely associated to the pathogenesis of PD. Wild-type α-syn has been proposed to have a propensity to form toxic species-oligomers and responsible for progressive neuron degeneration. Although α-syn is widely abundant in the central nervous system, the expression pattern was reported various in different brain region. In order to study how α-syn effects in different tissue region and contri...[ Read more ]

Parkinson’s disease (PD) is the most secondary neurodegenerative disease in the world. The most obvious symptoms in clinic are movement-related, which companies a selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of intraneuronal Lewy bodies (LBs) in pathology. Alpha-synuclein (α-syn) as a major structural component in LBs was considered closely associated to the pathogenesis of PD. Wild-type α-syn has been proposed to have a propensity to form toxic species-oligomers and responsible for progressive neuron degeneration. Although α-syn is widely abundant in the central nervous system, the expression pattern was reported various in different brain region. In order to study how α-syn effects in different tissue region and contributes to LBs formation and neuron degeneration, I approached Cre-loxP system, utilized the function of CL1 on protein oligomerization, developed two loxP-flanked transgenic mouse lines, one carried WT α-syn gene, another one carried WT α-syn-CL1 gene. These two mouse lines could be used to active α-syn expression in any tissue by crossbreeding with different Cre mouse line as long as the Cre was under the control of a tissue-specific promoter. Since DA neurons were preferentially degenerated in PD cases, I firstly activated α-syn expression in DA neurons by applying DAT^IRESCre mouse line. From observation and studies on DAT^cre+/-;SYN^+/- and DAT^cre+/-;SYN-CL1^+/- double hemizygous mice at different age stage, I found both two α-syn-expressing mice displayed motor deficits companied with striatal dopamine reduction and DA neuron loss. More important, I found α-syn aggregates-like particles were appeared within DA neurons and become prominent over time, and ubiquitin as another major component in LBs was also associated with this process. All phenotypes observed in α-syn-expressing mice suggested a close link to DA neuron-specific α-syn expression, and DA neurons in turn create a certain environment that may facilitate α-syn aggregation.