Chitinases as a Novel Therapeutic Target in Parkinson's Disease

Parkinson’s disease (PD) is a debilitating neurodegenerative disease characterized primarily by physical impairments such as tremors, poor balance, and bradykinesia; however, some individuals with PD will additionally experience numerous nonmotor symptoms such as dementia, depression, and sleep disturbances amongst various other life-altering ailments. Two of the key pathological hallmarks of PD include the death of melanated dopaminergic neurons in the nigrostriatal pathway and the accumulation of Lewy bodies, which are primarily composed of aggregates of the protein α-synuclein (α-syn). Interestingly, members of the chitinase protein family, namely chitinase-3-like protein-1 (L1), have heightened concentrations in a number of neurodegenerative diseases other than PD. To investigate the specific role L1 plays in PD etiology, we evaluated if astrocytic L1 expression was elevated in postmortem brain tissue of PD patients as well as in an α-syn overexpression rat model, and further tested if manipulating astrocytic-specific L1 expression correlated with neuroinflammation and nigral neuronal degeneration in the model. Preliminary histological analysis has shown increased levels of L1 expression in the α-syn model before neuronal loss occurs, and in human tissue, L1 was found to be significantly increased in the postmortem tissue of individuals with PD versus non-diseased controls. Investigations in identifying an astrocytic-specific virus capsid and manipulating L1 expression in the α-syn model are ongoing. This preliminary data thus far supports that increased astrocytic expression of L1 is associated with PD pathology.