ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Synaptic Location Is a Determinant of the Detrimental Effects of alpha-Synuclein Pathology to Glutamatergic Transmission in the Basolateral Amygdala
Publication: α-Synuclein in mouse brain is not ubiquitously expressed among glutamatergic axon terminals in the basolateral amygdala (BLA). This work looks at the distinctive characteristics between neuronal subtypes to understand which ar emore vulnerable to α-Synuclein aggregation and how this in turn could impact the entire circuit signaling. View the original preprint.
Synaptic location is a determinant of the detrimental effects of α-synuclein pathology to glutamatergic transmission in the basolateral amygdala
αSyn expression is restricted in a subset of glutamatergic synapses in BLA and its aggregation decreases cortico-BLA transmission through both gained toxicity and loss of normal function. These results might be relevant to the reduced cortical control of amygdala function that has been associated with psychiatric deficits in PD.
Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation
Published: Nuclear alpha-synuclein may play a role in the pathogenesis of PD. To study this, the authors engineered SncaNLS mice that exhibit endogenous alpha-synuclein in the nucleus. After behavioral, histological, and biochemical analysis of the mice, the authors found that chronic nuclear alpha-synuclein can create toxic cellular phenotypes, independent of aggregation.
Preprint: Decreasing alpha-synuclein levels is a potential therapeutic approach for synuleinopathies. The authors identified CDK14 regulates alpha-synuclein and show reduction of CDK14 in two different PD mouse models reduces alpha-synuclein and PD-like characteristics. They also demonstrate that inhibiting CDK14 with a drug lowers alpha-synuclein burdens in rodent and human neurons.