Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease
The presence of possibly toxic forms of intracellular α-synuclein, binding of aggregated α-synuclein and monomeric Aβ, and the potential co-localization of α-synuclein with intracellular neurofibrillary tangles as well as Aβ plaques in the brain could be the main causes in serious clinical symptoms...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223004744 |
| _version_ | 1797776670213537792 |
|---|---|
| author | Hong-Bin Cai Ming-Ming Li Tian Ting Min Yao Ya-Wen Pan Rupo Sui |
| author_facet | Hong-Bin Cai Ming-Ming Li Tian Ting Min Yao Ya-Wen Pan Rupo Sui |
| author_sort | Hong-Bin Cai |
| collection | DOAJ |
| description | The presence of possibly toxic forms of intracellular α-synuclein, binding of aggregated α-synuclein and monomeric Aβ, and the potential co-localization of α-synuclein with intracellular neurofibrillary tangles as well as Aβ plaques in the brain could be the main causes in serious clinical symptoms mostly developed in Alzheimer’s disease (AD) patients. Amyloid formation of α-synuclein can also induce neurotoxic effects through stimulation of endoplasmic reticulum stress (ERS). Therefore, the inhibition of protein aggregation can be of great importance for the control of pathophysiology of AD. Here, we assessed the use of sesamol as bioactive small molecule in inhibition of α-synuclein fibrillogenesis and neurotoxicity by different biophysical [ThT/Nile red/Congo red (CR)/circular dichroism (CD)] and cellular (MTT and qRT-PCR) analyses. From the spectroscopic analyses, we found that sesamol displays potential effect on the inhibiting the α-synuclein fibril formation. Also, sesamol showed no significant neurotoxicity and co-incubation of α-synuclein with sesamol apparently mitigated the ERS-mediated apoptosis induced by α-synuclein amyloids through regulation of IRE1, PERK, ATF6, and caspase-3 mRNA. Overall, sesamol-based compounds can be further developed and assessed for the regulation of pathophysiology of AD in which α-synuclein amyloids are predominantly involved. |
| first_indexed | 2024-03-12T22:54:09Z |
| format | Article |
| id | doaj.art-9daa9a742cbd4edcbeffd8ef94c92c07 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-12T22:54:09Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-9daa9a742cbd4edcbeffd8ef94c92c072023-07-20T04:37:54ZengElsevierArabian Journal of Chemistry1878-53522023-09-01169105012Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's diseaseHong-Bin Cai0Ming-Ming Li1Tian Ting2Min Yao3Ya-Wen Pan4Rupo Sui5Department of Neurology Lanzhou University Second Hospital, Lanzhou 730030, China; Institute of Neurology, Lanzhou University, Lanzhou 730030, ChinaDepartment of Neurology Lanzhou University Second Hospital, Lanzhou 730030, ChinaDepartment of Neurology Lanzhou University Second Hospital, Lanzhou 730030, ChinaDepartment of Neurology Lanzhou University Second Hospital, Lanzhou 730030, ChinaInstitute of Neurology, Lanzhou University, Lanzhou 730030, China; Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou 730030, China; Corresponding author at: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, No.82, Cuiyingmen, Chengguan District, Lanzhou City 730000, Gansu Province, China.Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121099, ChinaThe presence of possibly toxic forms of intracellular α-synuclein, binding of aggregated α-synuclein and monomeric Aβ, and the potential co-localization of α-synuclein with intracellular neurofibrillary tangles as well as Aβ plaques in the brain could be the main causes in serious clinical symptoms mostly developed in Alzheimer’s disease (AD) patients. Amyloid formation of α-synuclein can also induce neurotoxic effects through stimulation of endoplasmic reticulum stress (ERS). Therefore, the inhibition of protein aggregation can be of great importance for the control of pathophysiology of AD. Here, we assessed the use of sesamol as bioactive small molecule in inhibition of α-synuclein fibrillogenesis and neurotoxicity by different biophysical [ThT/Nile red/Congo red (CR)/circular dichroism (CD)] and cellular (MTT and qRT-PCR) analyses. From the spectroscopic analyses, we found that sesamol displays potential effect on the inhibiting the α-synuclein fibril formation. Also, sesamol showed no significant neurotoxicity and co-incubation of α-synuclein with sesamol apparently mitigated the ERS-mediated apoptosis induced by α-synuclein amyloids through regulation of IRE1, PERK, ATF6, and caspase-3 mRNA. Overall, sesamol-based compounds can be further developed and assessed for the regulation of pathophysiology of AD in which α-synuclein amyloids are predominantly involved.http://www.sciencedirect.com/science/article/pii/S1878535223004744α-SynucleinSesamolAmyloidInhibitionNeurotoxicity |
| spellingShingle | Hong-Bin Cai Ming-Ming Li Tian Ting Min Yao Ya-Wen Pan Rupo Sui Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease Arabian Journal of Chemistry α-Synuclein Sesamol Amyloid Inhibition Neurotoxicity |
| title | Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease |
| title_full | Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease |
| title_fullStr | Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease |
| title_full_unstemmed | Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease |
| title_short | Sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer's disease |
| title_sort | sesamol as a potential small molecule in inhibiting the induction of neurotoxic amyloids fibrils involved in the pathophysiology of alzheimer s disease |
| topic | α-Synuclein Sesamol Amyloid Inhibition Neurotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223004744 |
| work_keys_str_mv | AT hongbincai sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease AT mingmingli sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease AT tianting sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease AT minyao sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease AT yawenpan sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease AT ruposui sesamolasapotentialsmallmoleculeininhibitingtheinductionofneurotoxicamyloidsfibrilsinvolvedinthepathophysiologyofalzheimersdisease |