Gangliosides, α-Synuclein, and Parkinson's Disease

Progress in Molecular Biology and Translational Science
Robert W Ledeen, Gusheng Wu

Abstract

This review addresses the role of α-synuclein (αSyn) in the etiopathology of Parkinson's disease (PD), with emphasis on its interaction with GM1 ganglioside. We begin with a brief review of some of the milestone discoveries that helped to elucidate PD neuropathology, including the fibrous inclusions of Lewy that characterize the degenerating dopaminergic neurons of the substantia nigra and the presence of αSyn as a major constituent of these Lewy bodies and neurites. This enabled Braak et al. to define the progressive nature of PD in developing their staging hypothesis which described the topographically predictable sequence of neuropathological changes giving rise to prodromal nonmotor symptoms that precede the classical motor dysfunctions. We recount recent studies demonstrating strong, specific binding of αSyn to GM1 that serves to inhibit fibril formation and the key role of N-acetylation of αSyn in enhancing GM1 binding and specificity. The consequences of insufficient GM1 are illustrated in a newly presented mouse model of PD based on partial deletion of this ganglioside due to heterologous disruption of B4galnt1 (GM2/GD2 synthase), such mice presenting accurate recapitulation of the PD phenotype. A key feature of these m...Continue Reading

Citations

May 5, 2020·Glycobiology·Krzysztof MikolajczykMarcin Czerwinski
Dec 22, 2019·International Journal of Molecular Sciences·Enamul Haque MojumdarEmma Sparr
Feb 6, 2020·International Journal of Molecular Sciences·Elena ChiricozziLaura Mauri
Mar 27, 2019·Molecular Neurobiology·Elena ChiricozziSandro Sonnino
Apr 25, 2020·International Journal of Molecular Sciences·Erika Di BiaseElena Chiricozzi
Dec 20, 2019·Scientific Reports·Elena ChiricozziSandro Sonnino
Mar 19, 2020·Neuropsychiatric Disease and Treatment·Shanshan HuJianghui Dong
Sep 24, 2020·International Journal of Molecular Sciences·Alex E RyckmanJagdeep S Walia
Feb 24, 2021·Glycoconjugate Journal·Elena ChiricozziSandro Sonnino
Jul 11, 2021·Neurochemical Research·Qwynn LandfieldMariko Saito
Jun 11, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yutaka ItokazuRobert K Yu
Nov 11, 2021·Glycoconjugate Journal·Inka BrockhausenJennifer Brockhausen
Nov 20, 2021·Biophysical Journal·Maria J SarmentoRadek Šachl

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