Publications by authors named "Prakhyat Mathur"
Article Synopsis
- Excessive fragmentation of mitochondria is linked to various diseases, particularly neurodegenerative disorders, highlighting the importance of maintaining mitochondrial health.
- The integrated stress response (ISR), a signaling pathway that consists of four eIF2α kinases, plays a key role in regulating mitochondrial shape and function under stress conditions.
- Activation of ISR kinases HRI or GCN2 can promote beneficial mitochondrial elongation and counteract fragmentation, suggesting that targeting the ISR might be a viable treatment approach for diseases associated with mitochondrial dysfunction.
Axon degeneration is an early pathological event in many neurological diseases. The identification of the nicotinamide adenine dinucleotide (NAD) hydrolase SARM1 as a central metabolic sensor and axon executioner presents an exciting opportunity to develop novel neuroprotective therapies that can prevent or halt the degenerative process, yet limited progress has been made on advancing efficacious inhibitors. We describe a class of NAD-dependent active-site SARM1 inhibitors that function by intercepting NAD hydrolysis and undergoing covalent conjugation with the reaction product adenosine diphosphate ribose (ADPR).
View Article and Find Full Text PDFThe NADase SARM1 is a central switch in injury-activated axon degeneration, an early hallmark of many neurological diseases. Here, we present cryo-electron microscopy (cryo-EM) structures of autoinhibited (3.3 Å) and active SARM1 (6.
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