A5054948196- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Toxoplasma gondii Research Studies
- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- Calcium signaling and nucleotide metabolism
- Advanced Glycation End Products research
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Ginkgo biloba and Cashew Applications
- Calpain Protease Function and Regulation
- Biomedical Research and Pathophysiology
- Phagocytosis and Immune Regulation
- Glycogen Storage Diseases and Myoclonus
- Neurogenetic and Muscular Disorders Research
- Immune Cell Function and Interaction
- Carbon and Quantum Dots Applications
- Pancreatic function and diabetes
Manipal Academy of Higher Education
2024-2025
Institute for Stem Cell Biology and Regenerative Medicine
2025
Memorial Sloan Kettering Cancer Center
2016-2022
Albert Einstein College of Medicine
2006-2019
Howard Hughes Medical Institute
2013-2014
Yale University
2013-2014
The Bronx Defenders
2011
California Liver Research Institute
2011
Chaperone-mediated autophagy (CMA) is a selective type of by which specific cytosolic proteins are sent to lysosomes for degradation. Substrate bind the lysosomal membrane through lysosome-associated protein 2A (LAMP-2A), one three splice variants lamp2 gene, and this binding limiting their degradation via CMA. However, mechanisms substrate uptake remain unknown. We report here that LAMP-2A organizes at into complexes different sizes. The assembly disassembly these very dynamic process...
Autophagy, a major degradative pathway for proteins and organelles, is essential survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to pathogenesis, although the underlying mechanisms are not well understood. Here, we identified characterized marked intraneuronal amyloid-β peptide/amyloid lysosomal system mouse model TgCRND8 similar that previously described brains. We further establish basis these pathologies involves defective...
Rates of autophagy, the mechanism responsible for lysosomal clearance cellular components, decrease with age. We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form by which particular cytosolic proteins are delivered to lysosomes after binding lysosome-associated membrane protein type 2A (LAMP-2A), receptor this pathway. CMA age because levels LAMP-2A. In work we investigated reasons reduced LAMP-2A While transcriptional rates remain...
Chaperone-mediated autophagy (CMA) is an intracellular catabolic pathway that mediates the degradation of a selective subset cytosolic proteins in lysosomes ([Dice, 2007][1]; [Cuervo, 2010][2]; [Kon and Cuervo, 2010][3]; [Orenstein 2010][4]). The term (or self-eating)
Lysosomal failure underlies pathogenesis of numerous congenital neurodegenerative disorders and is an early progressive feature Alzheimer9s disease (AD) pathogenesis. Here, we report that lysosomal dysfunction in Down ayndrome (trisomy 21), a neurodevelopmental disorder form onset AD, requires the extra gene copy amyloid precursor protein (APP) specifically mediated by β cleaved carboxy terminal fragment APP (APP-βCTF, C99). In primary fibroblasts from individuals with DS, degradation...
Cystatin C (CysC) expression in the brain is elevated human patients with epilepsy, animal models of neurodegenerative conditions, and response to injury, but whether up-regulated CysC a manifestation neurodegeneration or cellular repair not understood. This study demonstrates that neuroprotective cultures exposed cytotoxic challenges, including nutritional-deprivation, colchicine, staurosporine, oxidative stress. While cysteine protease inhibitor, cathepsin B inhibition was required for...
The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and become an important therapeutic target for other neurodegenerative diseases. We recently observed broad effects stimulating proteolysis TgCRND8 mouse model that exhibits defective autophagic substrates, robust intralysosomal amyloid-β peptide (Aβ) accumulation,...
Mechanisms involved with degeneration of motor neurons in amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease) are poorly understood, but genetically inherited forms, comprising ∼10% the cases, potentially informative. Recent observations that several forms ALS involve RNA binding proteins TDP43 and FUS raise question as to whether metabolism is generally disturbed ALS. Here we conduct whole transcriptome profiling from a mouse strain, transgenic for mutant human SOD1 (G85R SOD1-YFP),...
Significance This is the first report, to our knowledge, of absence lipofuscin, “aging pigment,” in a setting motor neuron neurodegenerative disease, mutant SOD1-linked ALS. Although initial hypothesis was that this must be due block autophagy/lysosome pathway, instead studies autophagy markers and ALS mice treated with chloroquine suggest opposite, there hyperactivity at least part mediated through MTORC1.
AbstractA subset of cytosolic proteins can be selectively degraded in lysosomes through chaperone-mediated autophagy. The lysosomal-membrane protein type 2A (LAMP-2A) acts as the receptor for substrates autophagy (CMA), which should undergo unfolding before crossing lysosomal membrane and reaching lumen degradation. Translocation is assisted by chaperones on both sides membrane, but actual steps involved this process characteristics translocation complex were, most part, unknown. We have now...
Cellular homeostasis depends on a multitude of cellular functions, which in turn depend the clearance damaged components for their maintenance. Lysosomes being one main sites recycling, are at frontline protein degradation, leads to generation building blocks, amino acids (AAs), within lysosomal lumen. However, fate these pool AAs only partly known. Recently, studies from our and other groups have led finding that AA can be stored lysosomes revealed homeostatic communication storages with...
Significance Cells can respond to starvation by up-regulating stress responses that promote the recycling or scavenging of essential nutrients. We identify a response allows cells store amino acid leucine within lysosomes when extracellular acids are scarce. This “storage” sequester an in support protein synthesis. find numerous trafficked through even concentrations high, suggesting constitutive flux is related starvation-induced storage.
Lysosomes primarily recognized as center for cellular ‘garbage-disposing-unit’, which has recently emerged a crucial regulator of metabolism. This organelle is well-known vital player in the pathology including neurodegenerative disorders. In pathological context, removal intracellular damaged misfolded proteins, organelles and aggregates are ensured by ‘Autophagy’ pathway, initially recognizes, engulfs seals toxic cargo at cytosolic environment. Thereafter cell completes task encapsulated...
Preparation of high-quality RNA from cells interest is critical to precise and meaningful analysis transcriptional differences among cell types or between the same type in health disease following pharmacologic treatments. In spinal cord, such preparation motor neurons, target many neurologic neurodegenerative diseases, complicated by fact that neurons represent <10% total population. Laser capture microdissection (LMD) has been developed address this problem. Here, we describe a protocol...
Lysosomal system dysfunction is well-established in affected neurons Alzheimer's disease (AD), and increasingly believed to have pathogenic significance. We implicated disrupted autophagy, an inducible lysosomal pathway for the turnover of cytoplasm organelles, development pathology as a link between amyloidogenesis neurodegeneration AD. Autophagy appears be compromised some neurodegenerative diseases such polyglutamine repeat diseases, possible therapy these study focus has been on...
Preparation of high-quality RNA from cells interest is critical to precise and meaningful analysis transcriptional differences among cell types or between the same type in health disease following pharmacologic treatments. In spinal cord, such preparation motor neurons, target many neurologic neurodegenerative diseases, complicated by fact that neurons represent <10% total population. Laser capture microdissection (LMD) has been developed address this problem. Here, we describe a protocol...