Identification of LAG3 as the α-synuclein Neuronal Transmission Receptor

Unmet Need: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and leads to slowness of movement, tremor, rigidity, and, in the later stages of PD, cognitive impairment. Pathologically, PD is characterized by the accumulation of α-synuclein in Lewy bodies and neurites. Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell spread or transmission of pathologic misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. The identification of LAG3 (lymphocyte-activation gene 3) as a receptor that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies. The underlying mechanisms and molecular entities responsible for the transmission of pathologic α-syn from cell to cell are not known. There is a major unmet need to identify agents that can modulate the activity of LAG3 to reduce the pathology of Parkinson’s disease.
Technical Details: JHU scientists identified LAG3 as an α-syn PFF receptor. JHU scientists discovered that depletion of LAG3 or antibodies to LAG3 substantially reduces the pathology set in motion by the transmission of pathologic α-syn. The identification of LAG3 as an α-synuclein PFF–binding protein provides a new target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.
Stage of development/data: Pre-clinical
Publications: Science. 2016 Sep 30;353(6307).

 

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