The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by pathogen-associated molecular patterns (PAMPs), NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-1 that are overproduced in many inflammatory disease conditions.
By interfering with mitochondrial plasticity, researchers have succeeded in attenuating brain metastases of HER2-expressing breast tumors. The authors wrote that their findings “highlight targeting mitochondrial dynamics is a viable therapeutic opportunity to limit both brain tumors and metastasis.”
Researchers from The Salk Institute have described a signaling pathway that sets off an unusual, autophagy-dependent cell death mechanism as a fail-safe for cells that have evaded senescence mechanisms. The scientists found a tumor suppression mechanism mediated by telomere signaling, which activated an innate immune response through mitochondrial and telomere complexes to eliminate cells with shortened telomeres.
Neurons are specialized cells with a high metabolic demand to fulfill their function, survive or keep a healthy half-life. In this sense, the anabolism and catabolism of proteins and lipids could be associated to different neurodegenerative diseases. At the 2022 annual meeting of the Society for Neuroscience, scientists reported the latest discoveries on neuron metabolic needs at a session on 'Powering Thoughts: The Regulation of Neuronal Energy Metabolism and Mitochondria.'
Researchers from the University of Zaragoza and Promontory Therapeutics Inc. have discovered that PT-112, which has a multimodal mechanism of action, could have different clinical applications in cancer treatment due to its effects on mitochondria in castration-resistant prostate cancer (CRPC). PT-112 is an immunogenic small molecule currently in phase II development in metastatic castration-resistant prostate cancer (mCRPC). The researchers designed PT-112 to target advanced solid tumors, such as thymus, small-cell, non-small-cell lung or CRPC.
Lucy Therapeutics Inc. has announced promising preclinical data for multiple compounds in its lead program for Parkinson's disease, including two lead small-molecule agents, LucyTx-1209 and LucyTx-1212.
Variants in a newly discovered microprotein affected the risk of Alzheimer’s disease more than any other known risk variant besides ApoE. The protein, dubbed SHMOOSE by its discoverers, was identified in a mitochondrial-wide association study (miWAS). The researchers reported their findings in the Sept. 21, 2022, issue of Molecular Psychiatry. The newly identified variant is not rare – it occurs in about a quarter of the Caucasian population, slightly more than the ApoE4 allele. Its effects are also not subtle – in their paper, the team estimated that those with the high-risk variant SHMOOSED47N were roughly 30% more likely to develop AD than those without.
Pretzel Therapeutics Inc. has launched with a $72.5 million series A financing to pioneer novel therapies to modulate mitochondrial function to treat rare genetic diseases and common diseases of aging.
Investigators at Northwestern University’s Feinberg School of Medicine have used a new mouse model of Parkinson’s disease to confirm a causal role for mitochondrial dysfunction in Parkinson’s disease. More surprisingly, the same model has called into question previously uncontroversial notions about the motor features that are PD’s most conspicuous feature.
