De novo identification of potent ingredients for proteasome activation in MT101-5 using an AI-driven approach.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the intracellular accumulation of α-synuclein (α-syn) protein within Lewy bodies, which are hallmark neuropathological lesions of α-synucleinopathies. Network analysis, incorporating prior knowledge such as biological pathways and gene expression data from patients with PD, was used to identify the pharmaceutically active ingredients of MT101-5 and elucidate their mechanisms of action related to proteasome activation in PD. To validate the artificial intelligence (AI) model's prediction that API-mediated α-syn aggregate clearance occurs through enhanced proteasome activity, we employed a reporter-based screening to assess proteasome function within the ubiquitin-proteasome system. Our findings demonstrated that diterpenes derived from Genkwae Flos in MT101-5 inhibited α-syn fibril formation by restoring proteasome activation through Nurr1 activity. Two diterpenoids mitigated behavioural deficits and dopaminergic neuron loss in mice subjected to subacute MPTP administration (30 mg/kg/day for 5 days). These results provide preliminary evidence supporting the therapeutic potential of the active ingredients in MT101-5 for the prevention or treatment of PD.

• Publication year

  2026

• Venue

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

• Publication date

  2026-02-10

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.biopha.2026.119094PMID 41671731
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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