Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease.

1. J Clin Invest. 2020 Aug 3;130(8):4195-4212. doi: 10.1172/JCI136174. Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease. Sarkar S(1), Nguyen HM(2), Malovic E(1), Luo J(1), Langley M(1), Palanisamy BN(1), Singh N(1), Manne S(1), Neal M(1), Gabrielle M(3), Abdalla A(1), Anantharam P(4), Rokad D(1), Panicker N(1), Singh V(2), Ay M(1), Charli A(1), Harischandra D(1), Jin LW(5), Jin H(1), Rangaraju S(6), Anantharam V(1), Wulff H(2), Kanthasamy AG(1). Author information: (1)Parkinson Disorders Research Laboratory, Department of Biomedical Sciences, Iowa State University (ISU), Ames, Iowa, USA. (2)Department of Pharmacology, School of Medicine, UCD, Davis, California, USA. (3)Department of Biochemistry, University of Western Ontario, London, Ontario, Canada. (4)Department of Veterinary Diagnostic and Production Animal Medicine, Veterinary Medicine Building, ISU, Ames, Iowa, USA. (5)M.I.N.D. Institute, Alzheimer's Disease Center, Department of Pathology and Laboratory Medicine, UCD, Davis, California, USA. (6)Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. Characterization of the key cellular targets contributing to sustained microglial activation in neurodegenerative diseases, including Parkinson's disease (PD), and optimal modulation of these targets can provide potential treatments to halt disease progression. Here, we demonstrated that microglial Kv1.3, a voltage-gated potassium channel, was transcriptionally upregulated in response to aggregated α-synuclein (αSynAgg) stimulation in primary microglial cultures and animal models of PD, as well as in postmortem human PD brains. Patch-clamp electrophysiological studies confirmed that the observed Kv1.3 upregulation translated to increased Kv1.3 channel activity. The kinase Fyn, a risk factor for PD, modulated transcriptional upregulation and posttranslational modification of microglial Kv1.3. Multiple state-of-the-art analyses, includ