A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease

Mol Neurobiol. 2024 Mar;61(3):1237-1270. doi: 10.1007/s12035-023-03604-4. Epub 2023 Sep 12.

Abstract

A neurodegenerative disorder (ND) refers to Huntington's disease (HD) which affects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varying degrees of neuroprotection in preclinical HD studies because of their antioxidant and anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy, and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.

Keywords: Herbal medicine; Huntington’s disease; Mitochondrial dysfunction; Natural compounds; Neurodegenerative disorders; Neuroprotective; Nutraceuticals.

Publication types

  • Review

MeSH terms

  • Acetylcholinesterase
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Biological Products* / therapeutic use
  • Disease Models, Animal
  • Huntington Disease* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Nitro Compounds / pharmacology
  • Propionates / pharmacology
  • Propionates / therapeutic use
  • Rats
  • Rats, Wistar

Substances

  • Acetylcholinesterase
  • Antioxidants
  • Biological Products
  • Nitro Compounds
  • Propionates
  • Neuroprotective Agents