Mitochondrial dysfunction in Kennedy's disease: a new pharmacological target?
Chong Wang1, Wei Chen1, Dan Miao1
11 Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, China ; 2 Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA.
Annals of Translational Medicine
|May 21, 2015
Summary
Kennedy's disease involves mitochondrial dysfunction and oxidative stress. L-carnitine treatment showed a 40% reduction in creatine kinase levels, suggesting therapeutic potential for this neurodegenerative disorder.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Kennedy's disease pathogenesis is linked to mitochondrial impairment and oxidative stress.
- Mitochondrial nutrient management in Kennedy's disease remains understudied.
Purpose of the Study:
- To investigate mitochondrial nutrient management in a Kennedy's disease patient.
- To assess the impact of L-carnitine treatment on clinical markers.
Main Methods:
- Clinical and electrophysiological assessment of a genetically confirmed Kennedy's disease patient.
- Measurement of plasma 8-hydroxydeoxyguanosine (8-OHdG) using ELISA.
- Intravenous L-carnitine (2 g/day) administration for two weeks.
Main Results:
- Patient exhibited elevated creatine kinase (CK) and androgen receptor (AR) CAG repeat expansion (50 repeats).
- Elevated plasma 8-OHdG levels were observed in the patient compared to family members.
- L-carnitine treatment led to a ~40% reduction in CK levels.
Conclusions:
- Mitochondrial dysfunction and oxidative stress are implicated in Kennedy's disease.
- Targeting mitochondrial dysfunction presents potential therapeutic strategies for Kennedy's disease.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
19.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.7K
01:30The Electron Transport Chain
21.7K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
21.7K
01:45Mitochondrial Membranes
17.9K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.9K
01:48ATP Synthase: Mechanism
19.0K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
19.0K
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
69
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
69
01:19Translocation of Proteins into the Mitochondria
13.8K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.8K