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The Emerging Landscape of Natural Small-molecule Therapeutics for Huntington's Disease

Shahnawaz Ali Bhat1, Shakir Ahamad2, Nawab John Dar3

  • 1Department of Zoology, Aligarh Muslim University, Aligarh, U.P., India.

Current Neuropharmacology
|February 16, 2023
PubMed

Insights

Huntington's disease (HD) is a fatal neurodegenerative disorder. Natural products show promise for disease modification by reducing oxidative stress and neuroinflammation, unlike current symptomatic treatments.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder characterized by neuronal loss.
  • It stems from an expanded polyglutamine (polyQ) in the huntingtin (HTT) gene, producing toxic mutant HTT (mHTT) protein.
  • Current treatments offer only symptomatic relief, highlighting the need for disease-modifying therapies.

Approach:

  • This review summarizes the pathogenesis of HD.
  • It focuses on natural products with clinical and pre-clinical anti-HD potential.
  • The review examines their therapeutic effects and neuroprotective mechanisms.

Key Points:

  • Natural products possess anti-inflammatory and antioxidant properties beneficial for HD.
  • They mitigate mHTT-induced oxidative stress and neuroinflammation.
  • They improve mitochondrial function and promote anti-apoptotic and pro-autophagic mechanisms for neuronal survival.

Conclusions:

  • Natural products represent a promising avenue for developing disease-modifying therapeutics for HD.
  • Their multifaceted neuroprotective mechanisms offer hope beyond symptomatic treatment.
  • Further research into natural products could revolutionize HD treatment strategies.

Keywords:
Huntington’s diseaseNatural productsdrug discoveryhuntingtin (HTT)moleculesneuroprotective mechanismstherapeutic interventions

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