Publication: THE FUNCTIONAL ROLE OF MIRO1 IN NLRP1 INFLAMMASOME-MEDIATED NEURONAL CELL DEATH
| dc.contributor.author | NG JIA HAO | |
| dc.date.accessioned | 2024-10-01T09:25:34Z | |
| dc.date.available | 2024-10-01T09:25:34Z | |
| dc.date.issued | 2024 | |
| dc.description.abstract | Background Alzheimer's disease (AD) is characterized by progressive cognitive decline in aging, a neurodegenerative disorder marked by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), resulting in synaptic dysfunction and neuronal loss. Recent research highlights the intricate interplay between mitochondrial dysfunction and the NLR family pyrin domain-containing 1 (NLRP1) inflammasome in AD pathogenesis, focusing on MIRO1, a mitochondrial Rho GTPase. MIRO1, crucial for mitochondrial transport, orchestrates NLRP1 inflammasome-mediated neuronal cell death in AD. Studies reveal MIRO1's role in activating the NLRP1 inflammasome in response to Aβ. Dysregulated mitochondrial dynamics, due to aberrant MIRO1, contribute to AD pathology, intensifying NLRP1 inflammasome activation, creating a vicious cycle of neuroinflammation and accelerating neuronal demise. This study elucidates MIRO1's functional role in Aβ-induced NLRP1 inflammasome-mediated neuronal pyroptosis and downstream signaling using Multidimensional Protein Identification Technology (MudPIT). Background Alzheimer's disease (AD) is characterized by progressive cognitive decline in aging, a neurodegenerative disorder marked by amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), resulting in synaptic dysfunction and neuronal loss. Recent research highlights the intricate interplay between mitochondrial dysfunction and the NLR family pyrin domain-containing 1 (NLRP1) inflammasome in AD pathogenesis, focusing on MIRO1, a mitochondrial Rho GTPase. MIRO1, crucial for mitochondrial transport, orchestrates NLRP1 inflammasome-mediated neuronal cell death in AD. Studies reveal MIRO1's role in activating the NLRP1 inflammasome in response to Aβ. Dysregulated mitochondrial dynamics, due to aberrant MIRO1, contribute to AD pathology, intensifying NLRP1 inflammasome activation, creating a vicious cycle of neuroinflammation and accelerating neuronal demise. This study elucidates MIRO1's functional role in Aβ-induced NLRP1 inflammasome-mediated neuronal pyroptosis and downstream signaling using Multidimensional Protein Identification Technology (MudPIT). MIRO1 knockout (KO) exacerbated MMP depolarization and tau hyperphosphorylation upon Aβ-induced NLRP1 activation on neuronal cells. However, MIRO1 KO did not elevate but downregulated the caspase-1 activation upon Aβ-induced NLRP1 activation on neuronal cells. MudPIT results showed that PSMC5 as one of the differentially upregulated genes when MIRO1 KO was introduced in Aβ-induced NLRP1-mediated pyroptosis through proteasome pathway in AD. Conclusion Results indicated that MIRO1 modulated MMP, tau production, and caspase-1 activation in response to Aβ-induced NLRP1 activation pyroptosis. PSMC5 was found to regulate MIRO1 through the proteasome pathway in AD, with Carfilzomib, a PSMC5 inhibitor, suggesting a potential therapeutic approach for AD. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/36753 | |
| dc.language.iso | en | |
| dc.publisher | IMU University | |
| dc.subject | Alzheimer Disease | |
| dc.subject | Aging | |
| dc.subject | Neurodegenerative Diseases | |
| dc.subject | Inflammasomes | |
| dc.title | THE FUNCTIONAL ROLE OF MIRO1 IN NLRP1 INFLAMMASOME-MEDIATED NEURONAL CELL DEATH | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |