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Parkinson Disease: HELP
Articles by George Essien Umanah
Based on 4 articles published since 2010
(Why 4 articles?)
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Between 2010 and 2020, George E. Umanah wrote the following 4 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson's disease. 2018

Kam, Tae-In / Mao, Xiaobo / Park, Hyejin / Chou, Shih-Ching / Karuppagounder, Senthilkumar S / Umanah, George Essien / Yun, Seung Pil / Brahmachari, Saurav / Panicker, Nikhil / Chen, Rong / Andrabi, Shaida A / Qi, Chen / Poirier, Guy G / Pletnikova, Olga / Troncoso, Juan C / Bekris, Lynn M / Leverenz, James B / Pantelyat, Alexander / Ko, Han Seok / Rosenthal, Liana S / Dawson, Ted M / Dawson, Valina L. ·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. · Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Neurology, Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. · Centre de recherche du CHU de Québec-Pavillon CHUL, Faculté de Médecine, Université Laval, Québec G1V 4G2, Canada. · Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. · Lou Ruvo Center for Brain Health, Neurological Institute, and Department of Neurology, Cleveland Clinic, Cleveland, OH 44195, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tdawson@jhmi.edu vdawson1@jhmi.edu. · Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ·Science · Pubmed #30385548.

ABSTRACT: The pathologic accumulation and aggregation of α-synuclein (α-syn) underlies Parkinson's disease (PD). The molecular mechanisms by which pathologic α-syn causes neurodegeneration in PD are not known. Here, we found that pathologic α-syn activates poly(adenosine 5'-diphosphate-ribose) (PAR) polymerase-1 (PARP-1), and PAR generation accelerates the formation of pathologic α-syn, resulting in cell death via parthanatos. PARP inhibitors or genetic deletion of PARP-1 prevented pathologic α-syn toxicity. In a feed-forward loop, PAR converted pathologic α-syn to a more toxic strain. PAR levels were increased in the cerebrospinal fluid and brains of patients with PD, suggesting that PARP activation plays a role in PD pathogenesis. Thus, strategies aimed at inhibiting PARP-1 activation could hold promise as a disease-modifying therapy to prevent the loss of dopamine neurons in PD.

2 Article GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers. 2018

Kim, Sangjune / Yun, Seung Pil / Lee, Saebom / Umanah, George Essien / Bandaru, Veera Venkata Ratnam / Yin, Xiling / Rhee, Peter / Karuppagounder, Senthilkumar S / Kwon, Seung-Hwan / Lee, Hojae / Mao, Xiaobo / Kim, Donghoon / Pandey, Akhilesh / Lee, Gabsang / Dawson, Valina L / Dawson, Ted M / Ko, Han Seok. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130. · Mckusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; hko3@jhmi.edu. · Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130. ·Proc Natl Acad Sci U S A · Pubmed #29311330.

ABSTRACT: Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers. Here, we show that accumulation of GSLs due to GBA1 deficiency decreases α-syn tetramers and related multimers and increases α-syn monomers in CRISPR-GBA1 knockout (KO) SH-SY5Y cells. Moreover, α-syn tetramers and related multimers are decreased in N370S

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.

4 Article Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. 2016

Mao, Xiaobo / Ou, Michael Tianhao / Karuppagounder, Senthilkumar S / Kam, Tae-In / Yin, Xiling / Xiong, Yulan / Ge, Preston / Umanah, George Essien / Brahmachari, Saurav / Shin, Joo-Ho / Kang, Ho Chul / Zhang, Jianmin / Xu, Jinchong / Chen, Rong / Park, Hyejin / Andrabi, Shaida A / Kang, Sung Ung / Gonçalves, Rafaella Araújo / Liang, Yu / Zhang, Shu / Qi, Chen / Lam, Sharon / Keiler, James A / Tyson, Joel / Kim, Donghoon / Panicker, Nikhil / Yun, Seung Pil / Workman, Creg J / Vignali, Dario A A / Dawson, Valina L / Ko, Han Seok / Dawson, Ted M. ·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 Neurology, 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. 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. Department of Physiology, Ajou University School of Medicine, Suwon 443-721, 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. Department of Neurology, Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. · 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. Johns Hopkins Institute for NanoBio Technology, Johns Hopkins University, Baltimore, MD 21218, USA. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, 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. Department of Physiology, 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. tdawson@jhmi.edu hko3@jhmi.edu vdawson1@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. Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA. tdawson@jhmi.edu hko3@jhmi.edu vdawson1@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. Johns Hopkins Institute for NanoBio Technology, Johns Hopkins University, Baltimore, MD 21218, 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. tdawson@jhmi.edu hko3@jhmi.edu vdawson1@jhmi.edu. ·Science · Pubmed #27708076.

ABSTRACT: Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity. Lack of LAG3 substantially delayed α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. The identification of LAG3 as a receptor that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.