A5062643343- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Molecular Biology Techniques and Applications
- Prion Diseases and Protein Misfolding
- Biotin and Related Studies
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Viral Infectious Diseases and Gene Expression in Insects
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Sphingolipid Metabolism and Signaling
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Dermatology and Skin Diseases
- ATP Synthase and ATPases Research
- Invertebrate Immune Response Mechanisms
- Ginkgo biloba and Cashew Applications
- Cardiac, Anesthesia and Surgical Outcomes
- Advanced Electrical Measurement Techniques
- Peptidase Inhibition and Analysis
- Power Quality and Harmonics
Savitribai Phule Pune University
2023-2024
National Centre for Cell Science
2019-2024
Cornell University
2007-2019
Stowers Institute for Medical Research
2006-2016
National Brain Research Centre
2016
Tata Institute of Fundamental Research
2006
Max Planck Institute for Biophysical Chemistry
2006
Microglia are the main immune cells of brain, and under some circumstances they can play an important role in removal fibrillar Alzheimer amyloid beta peptide (fAbeta). Primary mouse microglia internalize fAbeta, but do not degrade it efficiently. We compared level lysosomal proteases J774 macrophages, which fAbeta efficiently, we found that actually contain higher levels many than macrophages. However, microglial lysosomes less acidic (average pH approximately 6), reducing activity enzymes...
Amyloids are ordered protein aggregates that typically associated with neurodegenerative diseases and cognitive impairment. By contrast, the amyloid-like state of neuronal RNA binding Orb2 in Drosophila was recently implicated memory consolidation, but it remains unclear what features this functional give rise to such diametrically opposed behaviour. Here, using an array biophysical, cell biological behavioural assays we have characterized structural from monomer amyloid state. Surprisingly,...
Incomplete lysosomal acidification in microglia inhibits the degradation of fibrillar forms Alzheimer's amyloid β peptide (fAβ). Here we show that primary a chloride transporter, ClC-7, is not delivered efficiently to lysosomes, causing incomplete acidification. ClC-7 protein synthesized by but it mistargeted and appears be degraded an endoplasmic reticulum-associated pathway. Activation with macrophage colony-stimulating factor induces trafficking leading increased fAβ degradation....
Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist Orb2A and Orb2B isoforms their formation is dependent on oligomerization isoform. with a mutation diminishing Orb2A's long-term memory but fails to maintain it over time. Since this plays crucial role in maintenance memory, here, we aim find what regulates oligomerization. In an immunoprecipitation-based screen, identify interactors Hsp40 Hsp70...
Aggregation of mutant forms Huntingtin is the underlying feature neurodegeneration observed in Huntington’s disorder. In addition to neurons, cellular processes non-neuronal cell types are also shown be affected. Cells expressing neurodegeneration–associated proteins show altered uptake ligands, suggestive impaired endocytosis, a manner as yet unknown. Using live imaging, we that clathrin-mediated endocytosis (CME) affected Drosophila hemocytes and mammalian cells containing aggregates. This...
Clathrin‐mediated endocytosis (CME) is essential for maintaining many basic cellular processes. We monitored the dynamics of clathrin in live Drosophila melanogaster hemocytes overexpressing light chain fused to enhanced green fluorescent protein (EGFP) using evanescent wave microscopy. Membrane‐associated clathrin‐coated structures (CCS) constitutively appeared at peripheral filopodial membrane, moved centripetally while growing intensity, before being eventually endocytosed within a few...
Abstract Protein aggregation is a common underlying feature of neurodegenerative disorders. Cells expressing neurodegeneration–associated mutant proteins show altered uptake ligands, suggestive impaired endocytosis, in manner as yet unknown. Using live cell imaging, we that clathrin-mediated endocytosis (CME) affected due to actin cytoskeletal organization the presence Huntingtin aggregates. Additionally, find cells containing aggregates are stiffer and less viscous than their wild-type...
Abstract Orb2 the Drosophila homolog of Cytoplasmic polyadenylation element binding protein (CPEB) forms prion-like oligomers. These oligomers consist Orb2A and Orb2B isoforms their formation are dependent on oligomerization isoform. with a mutation diminishing Orb2A’s long-term memory but fails to maintain it over time. Since, this plays crucial role in maintenance memory, here we aim find what regulates oligomerization. In an immunoprecipitation-based screen, identify interactors Hsp40...
Abstract Alzheimer’s disease (AD) is characterized by the accumulation of amyloid plaques surrounded microglia. In cell culture, microglia internalize fibrillar β-amyloid but do not degrade it efficiently. Unactivated have a relatively high lysosomal pH, which impairs activity proteases. Previous studies showed that activation with macrophage colony stimulating factor decreases pH and enhances degradation. We investigated role protease tripeptidyl peptidase 1 (TPP1) in culture mouse model...
Abstract Tau hyperphosphorylation is one of the major causes Alzheimer’s disease pathology. The abnormal phosphorylation curtails physiological function microtubule stabilization and renders it more prone to aggregation. Apart from its in cytoplasm, attributed play a role nucleus. Nuclear dependent on residue-specific phosphorylation. We studied effect green tea polyphenol, EGCG, formaldehyde-induced kinase CDK5. Interestingly, we observed unique localization phospho-Tau (AT 8 AT 100)...
<title>Abstract</title> Huntington’s disease (HD) is a rare neurodegenerative caused due to aggregation of Huntingtin (HTT) protein. This study involves cloning 40 DnaJ chaperones from Drosophila, and overexpressing them in yeasts fly models HD. Accordingly, were catalogued as enhancers or suppressors based on their growth phenotypes properties. 2 the that came up targets CG5001 P58IPK. Protein slow phenotype was rescued yeasts, S2 cells, Drosophila transgenic lines HTT103Q with these...
Abstract The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and condensation. Mutations proteins give rise to disease collectively referred as Cohesinopathies. major cause of Cohesinopathies arise due defects associated with gene expression, that developmental disorders. In this study, we have used Saccharomyces cerevisiae mimic the Cohesinopathy disorder Roberts syndrome mutations ( eco1W216G ) homologous humans (esco2). Our...
Abstract Huntington’s disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While Htt amyloid aggregates are known to affect many cellular processes, its role translation not addressed. Here we report pathogenic expression causes protein synthesis deficit cells. We find functional prion-like protein, regulator Orb2 be sequestered aggregates. Coexpression of can partially rescue lethality associated with expanded Htt. These...