Lipase regulation of cellular fatty acid homeostasis as a Parkinson’s disease therapeutic strategy View Full Text


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Article Info

DATE

2022-06-09

AUTHORS

Saranna Fanning, Haley Cirka, Jennifer L. Thies, Jooyoung Jeong, Sarah M. Niemi, Joon Yoon, Gary P. H. Ho, Julian A. Pacheco, Ulf Dettmer, Lei Liu, Clary B. Clish, Kevin J. Hodgetts, John N. Hutchinson, Christina R. Muratore, Guy A. Caldwell, Kim A. Caldwell, Dennis Selkoe

ABSTRACT

Synucleinopathy (Parkinson’s disease (PD); Lewy body dementia) disease-modifying treatments represent a huge unmet medical need. Although the PD-causing protein α-synuclein (αS) interacts with lipids and fatty acids (FA) physiologically and pathologically, targeting FA homeostasis for therapeutics is in its infancy. We identified the PD-relevant target stearoyl-coA desaturase: inhibiting monounsaturated FA synthesis reversed PD phenotypes. However, lipid degradation also generates FA pools. Here, we identify the rate-limiting lipase enzyme, LIPE, as a candidate target. Decreasing LIPE in human neural cells reduced αS inclusions. Patient αS triplication vs. corrected neurons had increased pSer129 and insoluble αS and decreased αS tetramer:monomer ratios. LIPE inhibition rescued all these and the abnormal unfolded protein response. LIPE inhibitors decreased pSer129 and restored tetramer:monomer equilibrium in αS E46K-expressing human neurons. LIPE reduction in vivo alleviated αS-induced dopaminergic neurodegeneration in Caenorhabditis elegans. Co-regulating FA synthesis and degradation proved additive in rescuing PD phenotypes, signifying co-targeting as a therapeutic strategy. More... »

PAGES

74

References to SciGraph publications

  • 1997-08. α-Synuclein in Lewy bodies in NATURE
  • 2006-03-08. Lipid droplets: a unified view of a dynamic organelle in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2016-11-09. Defects in trafficking bridge Parkinson's disease pathology and genetics in NATURE
  • 2011-08-14. α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation in NATURE
  • 2015-06-16. Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation in NATURE COMMUNICATIONS
  • 2011-01-19. A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language in GENOME BIOLOGY
  • 2008-02. Membrane lipids: where they are and how they behave in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2015-11-26. Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells in CELL DEATH & DISEASE
  • 2020-01-20. Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain in NATURE NEUROSCIENCE
  • 2011-05-26. Induction of human neuronal cells by defined transcription factors in NATURE
  • 2011-08-23. Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus in NATURE COMMUNICATIONS
  • 2004. Interactions among α-synuclein, dopamine, and biomembranes in JOURNAL OF MOLECULAR NEUROSCIENCE
  • 2020-01-03. Parkinson’s disease: proteinopathy or lipidopathy? in NPJ PARKINSON'S DISEASE
  • 2019-06-24. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes in NATURE NEUROSCIENCE
  • 2018-06-15. Genetic fine-mapping of the Iowan SNCA gene triplication in a patient with Parkinson’s disease in NPJ PARKINSON'S DISEASE
  • 2017-04-10. Integrated molecular landscape of Parkinson’s disease in NPJ PARKINSON'S DISEASE
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    URI

    http://scigraph.springernature.com/pub.10.1038/s41531-022-00335-6

    DOI

    http://dx.doi.org/10.1038/s41531-022-00335-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1148543463

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35680956


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