The mechanistic target of rapamycin signaling pathway
The nuclear pore complex (NPC) is the single gateway between the nucleus and the cytoplasm, and in healthy cells there is a size threshold for passive diffusion across the NPC. In aging and disease, the …
Acute-on-chronic liver failure (ACLF) is a severe liver syndrome marked by systemic inflammation and high mortality, often complicated by autophagy impairment and mitochondrial dysfunction. This study investigates atractylenolide I (AT-1), a compound from Atractylodes macrocephala, …
Aortic dissection (AD) is a catastrophic cardiovascular syndrome with an in-hospital mortality of more than 90%. We previously identified oxidative inactivation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) at cysteine 674 (C674) as a driver of …
Resistance to therapeutic agents represents a critical barrier in the clinical management of triple-negative breast cancer (TNBC), necessitating novel therapeutic strategies. We discovered that mammalian target of rapamycin (mTOR) and glutaminase 1 (GLS1) mediated glutamine …
Ribosomal protein S6 kinase 1 (S6K1) is a master regulator of cell growth and metabolism and a primary effector of the mTOR signaling pathway. Given its central role in cancer and metabolic diseases, S6K1 is …
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid {beta} fibrils (A{beta}) within walls of the cerebrovasculature and contributes to intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in patients with Alzheimers disease (AD) …
Tauopathies are neurodegenerative diseases characterized by the presence of hyperphosphorylated tau (p-tau) and neurofibrillary tangles. Autophagy is a critical self-degradation mechanism that preserves cellular homeostasis and function, including the clearance of misfolded proteins. Autophagy is …
BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with proximal tubule fibrosis being a key pathological feature. Our previous study identified significant upregulation of cytosolic nonspecific dipeptidase 2 (CNDP2) in …
AIMS: Numerous preclinical studies suggested that targeted inhibition of mammalian target of rapamycin (mTOR) may be beneficial for the treatment of osteoporosis. However, the relevance of these findings to human populations remains unclear. We hypothesized …
Cellular metabolism is precisely regulated in response to nutrient availability. As an extremely energy-consuming anabolic process, ribosome biogenesis should be tightly controlled in response to nutrient supply. However, how the nucleolus responds to different nutrient …
Researchers built a computer simulation of how aging works in the body and tested which combination of four existing drugs (semaglutide, SGLT2 inhibitors, metformin, and rapamycin) might slow aging most effectively. The model suggests that …
Abstract Background TNBC lacks clearly defined molecular targets, so chemotherapy remains the standard approach despite resistance, toxicity, and high relapse rates. New, less toxic therapeutic options are urgently needed. This study evaluated the anticancer potential …
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, highlighting the urgent requirement for innovative therapeutic strategies. Cytisine N-methylene-(4',5,7-trihydroxy)-isoflavone (named CNI3), a natural derivative of cytisine N-isoflavone isolated from Sophora alopecuroides …
Researchers found that a protein called pitp-1 acts as a brake on longevity by activating mTOR signaling—a key aging pathway. Disabling pitp-1 in neurons extended lifespan, improved muscle function, and boosted stress resistance in C. …
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by demyelination, neuroinflammation, and progressive neurodegeneration. The mechanistic target of rapamycin (mTOR) pathway plays a key role in regulating immune responses, cell metabolism, autophagy, and repair …
Adult stem cells are essential for maintaining tissue homeostasis and facilitating tissue repair. The ability of aged stem cells to generate functional progeny declines, which is closely associated with the onset and progression of age-related …
Biallelic pathogenic variants in STRADA (STE20-related adaptor alpha), an upstream regulator of the mechanistic target of rapamycin (mTOR) pathway, result in megalencephaly, drug-resistant epilepsy, and severe intellectual disability. This study explores how mTOR pathway hyperactivity …
Researchers gave aging mice rapamycin and found it prevented the normal decline in movement and motor control, with females benefiting more than males. The benefits appear linked to reduced oxidative stress and cellular stress in …
PLA2G6-associated neurodegeneration (PLAN) is a rare progressive disorder caused by mutations in PLA2G6, which encodes calcium-independent phospholipase A2, an enzyme required for phospholipid remodeling and membrane lipid homeostasis through the Lands cycle. Although mitochondrial dysfunction …
Dedifferentiated liposarcoma is a rare mesenchymal malignancy driven by amplification of chromosome 12q13-15, which includes the oncogenes CDK4 and MDM2. CDK4 amplification provides a rationale for targeted therapy with CDK4/6 inhibitors, and abemaciclib has shown …