Title:
USE OF PDH INHIBITORS IN TREATMENT OF NEURODEGENERATIVE DISEASES
Document Type and Number:
WIPO Patent Application WO/2024/029678
Kind Code:
A1
Abstract:
The present invention relates to a use of PDH inhibitors in the treatment of neurodegenerative diseases, and according to the present invention, in a DJ-1 deletion Parkinson's disease Drosophila model, by activation of PDK, promotion of PDK expression through DJ-1 and HIF-1, inhibition of PDP, or genetic and pharmacological inhibition of PDH using PDH inhibitors, sensitivity to ROS was lowered, and death of dopaminergic neurons was significantly reduced, and accordingly, the PDH inhibitors can be used in the prevention or treatment of neurodegenerative diseases.
Inventors:
KOH HYONGJONG (KR)
LEE YOONJEONG (KR)
KIM JAEHYEON (KR)
KANG KYONG-HWA (KR)
LEE YOONJEONG (KR)
KIM JAEHYEON (KR)
KANG KYONG-HWA (KR)
Application Number:
PCT/KR2023/001875
Publication Date:
February 08, 2024
Filing Date:
February 09, 2023
Export Citation:
Assignee:
UNIV DONG A RES FOUND FOR IND ACAD COOP (KR)
International Classes:
A61K31/20; A23L33/10; A61P25/28; G01N33/50
Foreign References:
| KR20170108967A | 2017-09-27 | |||
| KR20050084027A | 2005-08-26 |
Other References:
DANILEVICIUTE EGLE, ZENG NI, CAPELLE CHRISTOPHE M., PACZIA NICOLE, GILLESPIE MARK A., KURNIAWAN HENRY, BENZARTI MOHANED, MERZ MYRI: "PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing", NATURE METABOLISM, vol. 4, no. 5, 26 May 2022 (2022-05-26), pages 589 - 607, XP093135191, ISSN: 2522-5812, DOI: 10.1038/s42255-022-00576-y
KUMAR JHA MITHILESH, JEON SANGMIN, SUK KYOUNGHO: "Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders", CURRENT NEUROPHARMACOLOGY, BENTHAM SCIENCE PUBLISHERS, HILVERSUM, NL, vol. 10, no. 4, 1 December 2012 (2012-12-01), NL , pages 393 - 403, XP093135193, ISSN: 1570-159X, DOI: 10.2174/157015912804143586
MENCKE PAULINE, BOUSSAAD IBRAHIM, ROMANO CHIARA D., KITAMI TOSHIMORI, LINSTER CAROLE L., KRÜGER REJKO: "The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson’s Disease", CELLS, vol. 10, no. 2, 7 February 2021 (2021-02-07), pages 347, XP093135195, ISSN: 2073-4409, DOI: 10.3390/cells10020347
LEE YOONJEONG, KIM JAEHYEON, KIM HYUNJIN, HAN JI EUN, KIM SOHEE, KANG KYONG-HWA, KIM DONGHOON, KIM JONG-MIN, KOH HYONGJONG: "Pyruvate Dehydrogenase Kinase Protects Dopaminergic Neurons from Oxidative Stress in Drosophila DJ-1 Null Mutants", MOLECULES AND CELLS, SEOUL, KR, vol. 45, no. 7, 1 July 2022 (2022-07-01), KR , pages 454 - 464, XP093135196, ISSN: 1016-8478, DOI: 10.14348/molcells.2022.5002
KUMAR JHA MITHILESH, JEON SANGMIN, SUK KYOUNGHO: "Pyruvate Dehydrogenase Kinases in the Nervous System: Their Principal Functions in Neuronal-glial Metabolic Interaction and Neuro-metabolic Disorders", CURRENT NEUROPHARMACOLOGY, BENTHAM SCIENCE PUBLISHERS, HILVERSUM, NL, vol. 10, no. 4, 1 December 2012 (2012-12-01), NL , pages 393 - 403, XP093135193, ISSN: 1570-159X, DOI: 10.2174/157015912804143586
MENCKE PAULINE, BOUSSAAD IBRAHIM, ROMANO CHIARA D., KITAMI TOSHIMORI, LINSTER CAROLE L., KRÜGER REJKO: "The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson’s Disease", CELLS, vol. 10, no. 2, 7 February 2021 (2021-02-07), pages 347, XP093135195, ISSN: 2073-4409, DOI: 10.3390/cells10020347
LEE YOONJEONG, KIM JAEHYEON, KIM HYUNJIN, HAN JI EUN, KIM SOHEE, KANG KYONG-HWA, KIM DONGHOON, KIM JONG-MIN, KOH HYONGJONG: "Pyruvate Dehydrogenase Kinase Protects Dopaminergic Neurons from Oxidative Stress in Drosophila DJ-1 Null Mutants", MOLECULES AND CELLS, SEOUL, KR, vol. 45, no. 7, 1 July 2022 (2022-07-01), KR , pages 454 - 464, XP093135196, ISSN: 1016-8478, DOI: 10.14348/molcells.2022.5002
Attorney, Agent or Firm:
WIE, Byoung-Gap (KR)
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