A5021959959- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Nuclear Receptors and Signaling
- Cellular transport and secretion
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Cannabis and Cannabinoid Research
- Lysosomal Storage Disorders Research
- Neurological disorders and treatments
- Calcium signaling and nucleotide metabolism
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Plant Gene Expression Analysis
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Neurogenesis and neuroplasticity mechanisms
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
Icahn School of Medicine at Mount Sinai
2016-2025
Allen Institute for Brain Science
2016-2025
Shandong University of Traditional Chinese Medicine
2024
New York Proton Center
2012-2019
Xiangya Hospital Central South University
2018
Central South University
2018
Neurology, Inc
2017
China Medical University
2009-2012
First Hospital of China Medical University
2009-2012
Washtenaw Community College
2012
The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that -/- mutant mice die early embryogenesis +/- suffer from high incidence spontaneous tumors. These tumors continue to express wild-type mRNA protein, establishing is haploinsufficient tumor suppressor gene. Beclin embryonic stem cells have severely altered autophagic response, whereas their apoptotic response serum withdrawal or UV light...
Autophagy is a regulated lysosomal degradation process that involves autophagosome formation and transport. Although recent evidence indicates basal levels of autophagy protect against neurodegeneration, the exact mechanism whereby this occurs not known. By using conditional knockout mutant mice, we report neuronal particularly important for maintenance local homeostasis axon terminals protection axonal degeneration. We show specific ablation an essential gene, Atg7, in Purkinje cells...
Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity VTA DA neurons, caused an up-regulated hyperpolarization-activated current (I(h)). Mice resilient stress, however, exhibit stable normal firing these Unexpectedly, had even larger I(h), which was...
Abstract Microglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing; however, the precise mechanisms remain poorly understood. Herein, we report a neuroprotective role for in clearance of neuron-released α-synuclein. Neuronal α-synuclein activates microglia, which turn engulf into autophagosomes degradation via selective autophagy (termed synucleinphagy). Synucleinphagy...
Abstract Background MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a miR-152 significantly down-regulated gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" miR-152. Although aberrant expression of been observed several types cancer, its pathophysiologic role relevance to tumorigenesis still largely unknown. The purpose this study was elucidate...
LRRK2 autophosphorylation on Ser 1292 may be a useful indicator of kinase activity, providing readout for screening candidate inhibitors.
PARK8/LRRK2 ( leucine-rich repeat kinase 2 ) was recently identified as a causative gene for autosomal dominant Parkinson's disease (PD), with LRRK2 mutation G2019S linked to the most frequent familial form of PD. Emerging in vitro evidence indicates that aberrant enzymatic activity protein carrying this can cause neurotoxicity. However, physiological and pathophysiological functions vivo remain elusive. Here we characterize two bacterial artificial chromosome (BAC) transgenic mouse strains...
Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and protection (N551K) mediate shared effects CD Parkinson’s disease.
This study aimed to elucidate the genetic causes underlying early-onset Parkinsonism (EOP) in a consanguineous Iranian family. To attain this, homozygosity mapping and whole-exome sequencing were performed. As result, homozygous mutation (c.773G>A; p.Arg258Gln) lying within NH2 -terminal Sac1-like inositol phosphatase domain of polyphosphoinositide synaptojanin 1 (SYNJ1), which has been implicated regulation endocytic traffic at synapses, was identified as disease-segregating mutation....
Disruption of proteostasis, or protein homeostasis, is often associated with aberrant accumulation misfolded proteins aggregates. Autophagy offers protection to cells by removing toxic aggregates and injured organelles in response proteotoxic stress. However, the exact mechanism whereby autophagy recognizes degrades aggregated has yet be elucidated. Mounting evidence demonstrates selectivity autophagy, which mediated through receptor (e.g. p62/SQSTM1) linking cargos autophagosomes. Here we...
Parkinson's disease (PD) is characterized pathologically by the formation of ubiquitin and α-synuclein (α-syn)-containing inclusions (Lewy bodies), dystrophic dopamine (DA) terminals, degeneration midbrain DA neurons. The precise molecular mechanisms underlying these pathological features remain elusive. Accumulating evidence has implicated dysfunctional autophagy, cell self-digestion neuroprotective pathway, as one pathogenic systems contributing to development idiopathic PD. Here we...
Cardiac autophagy is inhibited in type 1 diabetes. However, it remains unknown if the reduced contributes to pathogenesis of diabetic cardiomyopathy. We addressed this question using mouse models with gain- and loss-of-autophagy. Autophagic flux was hearts when measured at multiple time points after diabetes induction by streptozotocin as assessed protein levels microtubule-associated light chain 3 form 2 (LC3-II) or GFP-LC3 puncta absence presence lysosome inhibitor bafilomycin A1....
Macroautophagy (autophagy) is a key catabolic pathway for the maintenance of proteostasis through constant digestion selective cargoes. The selectivity autophagy mediated by receptors that recognize and recruit cargoes to autophagosomes. SQSTM1/p62 prototype receptor, which commonly found in protein aggregates associated with major neurodegenerative diseases. While accumulation SQSTM1 implicates disturbance pathway, pathogenic mechanism contributes impaired degradation remains poorly...
Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from microglia. Cerebellar microglial identity was driven by CSF-1R ligand CSF-1, independently of alternate ligand, IL-34. Accordingly, CSF-1 depletion Nestin+ cells led to severe transcriptional alterations microglia, while remained intact....