A5003671931- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- Developmental Biology and Gene Regulation
- Neurobiology and Insect Physiology Research
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Hippo pathway signaling and YAP/TAZ
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Receptors and Signaling
- RNA and protein synthesis mechanisms
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Cholinesterase and Neurodegenerative Diseases
- ATP Synthase and ATPases Research
- Amyotrophic Lateral Sclerosis Research
- Sirtuins and Resveratrol in Medicine
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- RNA modifications and cancer
- Nerve injury and regeneration
- Neurogenetic and Muscular Disorders Research
Stanford University
2015-2024
Stanford Medicine
2011-2023
Palo Alto University
2016
Second Artillery General Hospital of Chinese People's Liberation Army
2014
The University of Texas at Austin
2012
Geriatric Research Education and Clinical Center
2004-2010
VA Palo Alto Health Care System
2004-2009
Fujita Health University
2005
Osaka University
2005
Cornell University
2005
Mutations in Pink1, a gene encoding Ser/Thr kinase with mitochondrial-targeting signal, are associated Parkinson's disease (PD), the most common movement disorder characterized by selective loss of dopaminergic neurons. The mechanism which Pink1 leads to neurodegeneration is not understood. Here we show that inhibition Drosophila (dPink1) function results energy depletion, shortened lifespan, and degeneration select indirect flight muscles muscle pathology was preceded mitochondrial...
Mitochondria form dynamic tubular networks that undergo frequent morphological changes through fission and fusion, the imbalance of which can affect cell survival in general impact synaptic transmission plasticity neurons particular. Some core components mitochondrial fission/fusion machinery, including dynamin-like GTPases Drp1, Mitofusin, Opa1, Drp1-interacting protein Fis1, have been identified. How fusion processes are regulated under normal conditions extent to defects involved various...
Mutations in Pten-induced kinase 1 (PINK1) are linked to early-onset familial Parkinson's disease (FPD). PINK1 has previously been implicated mitochondrial fission/fusion dynamics, quality control, and electron transport chain function. However, it is not clear how these processes interconnected whether they sufficient explain all aspects of pathogenesis. Here we show that also controls motility. In Drosophila, downregulation dMiro or other components the machinery rescued dPINK1 mutant...
Parkinson's disease (PD) is the most common movement disorder characterized by dopaminergic dysfunction and degeneration. The cause of PD cases unknown, although postmortem studies have implicated involvement oxidative stress. identification familial PD-associated genes offers opportunity to study mechanisms pathogenesis in model organisms. Here, we show that DJ-1A, a Drosophila homologue gene DJ-1, plays an essential role stress response neuronal maintenance. Inhibition DJ-1A function...
Calcium (Ca2+) homeostasis is essential for neuronal function and survival. Altered Ca2+ has been consistently observed in neurological diseases. How achieved various cellular compartments of disease-relevant cell types not well understood. Here we show Drosophila Parkinson's disease (PD) models that transport from the endoplasmic reticulum (ER) to mitochondria through ER-mitochondria contact site (ERMCS) critically regulates mitochondrial (mito-Ca2+) dopaminergic (DA) neurons, PD-associated...
PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which pathogenesis Parkinson's disease (PD) is increasingly being appreciated. However, how PINK1/Parkin influences function not well understood, exact role this controlling dynamics remains controversial. Here we used mammalian primary neurons examine regulating function. In rat hippocampal neurons, PINK1 or overexpression resulted increased number, smaller size...
Mutations in the LRRK2 gene are most common genetic cause of familial Parkinson's disease (PD). However, its physiological and pathological functions unknown. Therefore, we generated several independent Drosophila lines carrying WT or mutant human (mutations kinase, COR LRR domains, resp.). Ectopic expression dopaminergic neurons caused their significant loss accompanied by complex age-dependent changes locomotor activity. Overall, ubiquitous increased lifespan fertility flies. these flies...
Mutations in PTEN-induced kinase 1 (PINK1), a mitochondrial Ser/Thr kinase, cause an autosomal recessive form of Parkinson's disease (PD), PARK6. To investigate the mechanism PINK1 pathogenesis, we used Drosophila Pink1 knockout (KO) model. In mitochondria isolated from Pink1-KO flies, respiration driven by electron transport chain (ETC) is significantly reduced. This reduction result decrease ETC complex I and IV enzymatic activity. As consequence, flies also display reduced ATP synthesis....
Neurofibrillary tangles (NFTs) are a characteristic neuropathological feature of Alzheimer's disease (AD), and molecular chaperones appear to be involved in the removal disease-associated hyperphosphorylated tau, primary component NFTs. Here, novel HSP90 inhibitors were used examine impact chaperone elevation on clearance different tau species transfected cells using unique quantitative assay. The reduced levels phosphorylated at proline-directed Ser/Thr sites (pS202/T205, pS396/S404)...
Abstract Background Parkinson's disease (PD) is the most common movement disorder. Extrapyramidal motor symptoms stem from degeneration of dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating without reversing or retarding progression. Although cause remains unknown, several pathogenic factors have been identified, which neuron (DN) death substantia nigra (SN). These include oxidative stress, mitochondrial dysfunction, inflammation and...
Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis Alzheimer's disease (AD); however, what pathological conditions trigger abnormality AD is not fully understood. A reduction number mitochondria axon has been implicated AD. In this study, we investigated whether how loss axonal promotes vivo. Using transgenic Drosophila expressing human tau, found that RNAi–mediated knockdown milton or Miro, an adaptor essential for transport...
Tau hyperphosphorylation is thought to underlie tauopathy. Working in a Drosophila tauopathy model expressing human mutant (hTauR406W, or Tau∗), we show that zinc contributes the development of toxicity through two independent actions: by increasing phosphorylation and, more significantly, directly binding Tau. Elimination amino acid substitution Cys residues has minimal effect on levels yet essentially eliminates toxicity. The zinc-binding-deficient Tau∗ (Tau∗C2A) and overexpression native...