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Article

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

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
*
Author to whom correspondence should be addressed.
Academic Editor: Lucian Hritcu
Molecules 2021, 26(12), 3736; https://doi.org/10.3390/molecules26123736
Received: 24 April 2021 / Revised: 12 June 2021 / Accepted: 15 June 2021 / Published: 19 June 2021
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. View Full-Text
Keywords: α-synuclein; Parkinson’s disease; seeded fibril formation α-synuclein; Parkinson’s disease; seeded fibril formation
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MDPI and ACS Style

Ghanem, S.S.; Fayed, H.S.; Zhu, Q.; Lu, J.-H.; Vaikath, N.N.; Ponraj, J.; Mansour, S.; El-Agnaf, O.M.A. Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity. Molecules 2021, 26, 3736. https://doi.org/10.3390/molecules26123736

AMA Style

Ghanem SS, Fayed HS, Zhu Q, Lu J-H, Vaikath NN, Ponraj J, Mansour S, El-Agnaf OMA. Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity. Molecules. 2021; 26(12):3736. https://doi.org/10.3390/molecules26123736

Chicago/Turabian Style

Ghanem, Simona S., Hend S. Fayed, Qi Zhu, Jia-Hong Lu, Nishant N. Vaikath, Janarthanan Ponraj, Said Mansour, and Omar M.A. El-Agnaf 2021. "Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity" Molecules 26, no. 12: 3736. https://doi.org/10.3390/molecules26123736

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