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Title: Conditional disruption of AMP kinase in dopaminergic neurons promotes Parkinson's disease-associated phenotypes in vivo
Authors: Hang, Liting
Wang, Ziyin
Foo, Aaron S. C.
Goh, Geraldine
Choong, Huey Ching
Thundyil, John
Xu, Shengli
Lam, Kong-Peng
Lim, Kah-Leong
Keywords: Science::Medicine
Issue Date: 2021
Source: Hang, L., Wang, Z., Foo, A. S. C., Goh, G., Choong, H. C., Thundyil, J., Xu, S., Lam, K. & Lim, K. (2021). Conditional disruption of AMP kinase in dopaminergic neurons promotes Parkinson's disease-associated phenotypes in vivo. Neurobiology of Disease, 161, 105560-.
Journal: Neurobiology of Disease 
Abstract: Emerging studies implicate energy dysregulation as an underlying trigger for Parkinson's disease (PD), suggesting that a better understanding of the molecular pathways governing energy homeostasis could help elucidate therapeutic targets for the disease. A critical cellular energy regulator is AMP kinase (AMPK), which we have previously shown to be protective in PD models. However, precisely how AMPK function impacts on dopaminergic neuronal survival and disease pathogenesis remains elusive. Here, we showed that Drosophila deficient in AMPK function exhibits PD-like features, including dopaminergic neuronal loss and climbing impairment that progress with age. We also created a tissue-specific AMPK-knockout mouse model where the catalytic subunits of AMPK are ablated in nigral dopaminergic neurons. Using this model, we demonstrated that loss of AMPK function promotes dopaminergic neurodegeneration and associated locomotor aberrations. Accompanying this is an apparent reduction in the number of mitochondria in the surviving AMPK-deficient nigral dopaminergic neurons, suggesting that an impairment in mitochondrial biogenesis may underlie the observed PD-associated phenotypes. Importantly, the loss of AMPK function enhances the susceptibility of nigral dopaminergic neurons in these mice to 6-hydroxydopamine-induced toxicity. Notably, we also found that AMPK activation is reduced in post-mortem PD brain samples. Taken together, these findings highlight the importance of neuronal energy homeostasis by AMPK in PD and position AMPK pathway as an attractive target for future therapeutic exploitation.
ISSN: 0969-9961
DOI: 10.1016/j.nbd.2021.105560
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
School of Biological Sciences 
Organisations: National University of Singapore
National Neuroscience Institute
Singapore Immunology Network, A*STAR
Rights: © 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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