2. Academic Validation
  3. Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity

Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity

  • Molecules. 2021 Jun 19;26(12):3736. doi: 10.3390/molecules26123736.
Simona S Ghanem 1,  Hend S Fayed 1 2,  Qi Zhu 3,  Jia-Hong Lu 3,  Nishant N Vaikath 1,  Janarthanan Ponraj 4,  Said Mansour 4,  Omar M A El-Agnaf 1 2
Affiliations

Affiliations

  • 1 Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 34110, Qatar.
  • 2 Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar.
  • 3 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
  • 4 Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar.
PMID: 34205249 DOI: 10.3390/molecules26123736
Abstract

The accumulation and aggregation of α-synuclein (α-syn) is the main pathologic event in Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-Syn-seeded fibril formation and its induced toxicity occupy a major role in PD pathogenesis. Thus, assessing compounds that inhibit this seeding process is considered a key towards the therapeutics of synucleinopathies. Using biophysical and biochemical techniques and seeding-dependent cell viability assays, we screened a total of nine natural compounds of alkaloid origin extracted from Chinese medicinal herbs. Of these compounds, synephrine, trigonelline, cytisine, harmine, koumine, peimisine, and hupehenine exhibited in vitro inhibition of α-syn-seeded fibril formation. Furthermore, using cell viability assays, six of these compounds inhibited α-syn-seeding-dependent toxicity. These six potent inhibitors of amyloid fibril formation and toxicity caused by the seeding process represent a promising therapeutic strategy for the treatment of PD and Other synucleinopathies.

Keywords

Parkinson’s disease; seeded fibril formation; α-synuclein.

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