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One potential strategy for treating Parkinson’s disease is to prevent the formation of intracellular inclusions comprised of misfolded alpha-synuclein in the brain.
In a paper in Neurobiology of Disease (online, 12 July 2017), researchers explored the effect of the antidepressant nortriptyline on the formation of alpha-synuclein[1]
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They first showed in vitro that the drug is able to bind directly to alpha-synuclein and interfere with its folding, inhibiting formation of toxic forms of the protein. In both in vitro and animal models they then showed that this led to reduced levels of accumulation, aggregation and neurotoxicity of alpha-synuclein.
Noting that nortriptyline is considered effective and safe for treating comorbid depression in Parkinson’s disease, the team suggested it could become a multi-functional compound to treat the disorder.
References
[1] Collier T, Srivastava K, Justman C et al. Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form. Neurobiol Dis 2017;106:191–204. doi: 10.1016/j.nbd.2017.07.007
