Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles by Stewart Neifert
Based on 3 articles published since 2010
(Why 3 articles?)
||||

Between 2010 and 2020, Stewart Neifert wrote the following 3 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice. 2018

Xiong, Yulan / Neifert, Stewart / Karuppagounder, Senthilkumar S / Liu, Qinfang / Stankowski, Jeannette N / Lee, Byoung Dae / Ko, Han Seok / Lee, Yunjong / Grima, Jonathan C / Mao, Xiaobo / Jiang, Haisong / Kang, Sung-Ung / Swing, Deborah A / Iacovitti, Lorraine / Tessarollo, Lino / Dawson, Ted M / Dawson, Valina L. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205; yulanxiong@ksu.edu vdawson@jhmi.edu tdawson@jhmi.edu. · Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685. · Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685. · Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702. · Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107. · Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107. · Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205. ·Proc Natl Acad Sci U S A · Pubmed #29386392.

ABSTRACT: Mutations in LRRK2 are known to be the most common genetic cause of sporadic and familial Parkinson's disease (PD). Multiple lines of LRRK2 transgenic or knockin mice have been developed, yet none exhibit substantial dopamine (DA)-neuron degeneration. Here we develop human tyrosine hydroxylase (TH) promoter-controlled tetracycline-sensitive LRRK2 G2019S (GS) and LRRK2 G2019S kinase-dead (GS/DA) transgenic mice and show that LRRK2 GS expression leads to an age- and kinase-dependent cell-autonomous neurodegeneration of DA and norepinephrine (NE) neurons. Accompanying the loss of DA neurons are DA-dependent behavioral deficits and α-synuclein pathology that are also LRRK2 GS kinase-dependent. Transmission EM reveals that that there is an LRRK2 GS kinase-dependent significant reduction in synaptic vesicle number and a greater abundance of clathrin-coated vesicles in DA neurons. These transgenic mice indicate that LRRK2-induced DA and NE neurodegeneration is kinase-dependent and can occur in a cell-autonomous manner. Moreover, these mice provide a substantial advance in animal model development for LRRK2-associated PD and an important platform to investigate molecular mechanisms for how DA neurons degenerate as a result of expression of mutant LRRK2.

2 Article Overexpression of Parkinson's Disease-Associated Mutation LRRK2 G2019S in Mouse Forebrain Induces Behavioral Deficits and α-Synuclein Pathology. 2017

Xiong, Yulan / Neifert, Stewart / Karuppagounder, Senthilkumar S / Stankowski, Jeannette N / Lee, Byoung Dae / Grima, Jonathan C / Chen, Guanxing / Ko, Han Seok / Lee, Yunjong / Swing, Debbie / Tessarollo, Lino / Dawson, Ted M / Dawson, Valina L. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine, Manhattan, Kansas 66506. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. · Department of Anatomy and Physiology, Kansas State University College of Veterinary Medicine , Manhattan, Kansas 66506. · Neural Development Section, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130; Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Soloman H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130; Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana 70130. ·eNeuro · Pubmed #28321439.

ABSTRACT: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified as an unambiguous cause of late-onset, autosomal-dominant familial Parkinson's disease (PD) and LRRK2 mutations are the strongest genetic risk factor for sporadic PD known to date. A number of transgenic mice expressing wild-type or mutant LRRK2 have been described with varying degrees of LRRK2-related abnormalities and modest pathologies. None of these studies directly addressed the role of the kinase domain in the changes observed and none of the mice present with robust features of the human disease. In an attempt to address these issues, we created a conditional LRRK2 G2019S (LRRK2 GS) mutant and a functionally negative control, LRRK2 G2019S/D1994A (LRRK2 GS/DA). Expression of LRRK2 GS or LRRK2 GS/DA was conditionally controlled using the tet-off system in which the presence of tetracycline-transactivator protein (tTA) with a CAMKII

3 Article PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival. 2017

Lee, Yunjong / Stevens, Daniel A / Kang, Sung-Ung / Jiang, Haisong / Lee, Yun-Il / Ko, Han Seok / Scarffe, Leslie A / Umanah, George E / Kang, Hojin / Ham, Sangwoo / Kam, Tae-In / Allen, Kathleen / Brahmachari, Saurav / Kim, Jungwoo Wren / Neifert, Stewart / Yun, Seung Pil / Fiesel, Fabienne C / Springer, Wolfdieter / Dawson, Valina L / Shin, Joo-Ho / Dawson, Ted M. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Mayo Graduate School, Neurobiology of Disease, Mayo Clinic, Jacksonville, FL 32224, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. Electronic address: vdawson@jhmi.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. Electronic address: jshin24@skku.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. Electronic address: tdawson@jhmi.edu. ·Cell Rep · Pubmed #28122242.

ABSTRACT: Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson's disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival.