Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases
Abstract
:1. Introduction
2. Mitochondria
3. Mitochondrial Dysfunction in Aging: Causes
4. Mitochondrial Dysfunction and Inflammation
5. Mitochondrial Dysfunction and Brain Aging
6. Role of Mitochondrial Dysfunction in Brain Aging Disorders
7. Huntington’s Disease
8. Mitochondrial Dysfunction in Models of Huntington’s Disease
9. Parkinson’s Disease
10. Mitochondrial Dysfunction in Models of Parkinson’s Disease
11. Alzheimer’s Disease
12. Mitochondrial Dysfunction in Models of Alzheimer’s Disease
13. Current Treatments of Mitochondrial Dysfunction
14. PGC-1α Expression
15. Caloric Restriction and Fasting Diets
16. Physical Exercise
17. Prevention of Drug-Induced Mitochondrial Toxicity
18. Dietary Supplements
18.1. Antioxidants
18.2. Vitamin D
18.3. Coenzyme Q
18.4. Melatonin
18.5. Herbal Medicine
19. Pharmacologics
20. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AD | Alzheimer’s Disease |
ADAF-1 | apoptotic protease activating factor-1 |
AET | aerobic exercise training |
ALP | autophagy-lysosomal pathway |
ApoE | apolipoprotein E |
APP | amyloid precursor protein |
ATP | adenosine triphosphate (energy) |
Aβ | amyloid-beta |
AβPP | amyloid beta protein precursor |
BBB | blood brain barrier |
Ca2+ | calcium |
CAT | catalase |
cGAMP | cyclic dinucleotide 2′3′-Cyclic GMP-AMP |
cGAS | cyclic GMP-AMP synthase |
CLPP | Clp protease proteolytic subunit |
CoQ | coenzyme Q/ubiquinone |
CoQ10 | coenzyme Q10 |
CR | caloric restriction |
DAMP | damage-associated molecular pattern |
DOPAC | 3,4-Dihydroxyphenylacetic acid |
ER | endoplasmic reticulum |
ETC | electron transport chain |
FPR | formyl-peptide receptor |
GHS | glutathione |
GPx | glutathione peroxidase |
GSC | germline stem cell |
H+ | protons |
H2O | water |
H2O2 | hydrogen peroxide |
HD | Huntington’s Disease |
HO• | hydroxyl radical |
HTT | huntingtin |
HVA | homovanillic acid |
IFN-I | type I interferon |
IMM | inner mitochondrial membrane |
IRF-3 | interferon regulatory factor 3 |
KDC | ketoglutarate dehydrogenase complex |
KI | knock-in |
KO | knock-out |
KRS | Kufor–Rakeb syndrome |
LONP | lon protease homologue |
MAO | monoamine oxidase |
MCU | mitochondrial calcium uniporter |
mDAMP | mitochondrial damage-associated molecular pattern |
MFRTA | mitochondrial free-radical theory of aging |
MI | myocardial infarction |
MPTP | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine |
mtDNA | mitochondrial DNA |
MTFMT | methionyl-tRNA formyltransferase |
mtROS | mitochondrial reactive oxygen species |
nDNA | nuclear DNA |
NFT | intracellular neurofibrillary tangle |
NLR | NOD-like receptor |
O2•− | superoxide radical |
OMM | outer mitochondrial membrane |
oxCL | oxidized cardiolipin |
OXPHOS | oxidative phosphorylation |
P2 | purinergic |
PAMP | pathogen-associated molecular pattern |
PD | Parkinson’s Disease |
PDC | pyruvate dehydrogenase complex |
PGC-1α | Peroxisome proliferator-activated receptor-γ coactivator |
PINK-1 | PTEN-induced kinase-1 |
PolgA | mtDNA polymerase-γ |
PRR | pattern recognition receptor |
PS1/2 | presenilin 1 or 2 |
pTAU | hyperphosphorylated tau |
RA | rheumatoid arthritis |
RET | resistance exercise training |
ROS | reactive oxygen species |
rRNA | ribosomal RNA |
SNpc | substantia nigra pars compacta |
SOD | superoxide dismutase |
TCA | tricarboxylic acid cycle |
TFAM | Transcription factor A mitochondrial |
TLR | toll-like receptor |
tRNA | transfer RNA |
UPS | Ubiquitin Proteasome System |
VDAC | voltage-dependent anion channel |
VDR | vitamin D receptor |
YAC | yeast artificial chromosome |
α-Syn | alpha-synuclein |
4-HNE | 4-hydroxynonenal |
5-Lox | 5-lypoxygenase |
6-OHDA | 6-hydroxydopamine |
8-OHdG | 8-oxo-2′-deoxyguanosine |
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Disorder | Genes Involved | Affected Mitochondrial Complex(es) | Associated Mitochondrial Dysfunction | Reference(s) |
---|---|---|---|---|
Huntington’s Disease | HTT | II, III, IV | Reduced functioning in mitochondrial ETC components; reduced ATP production; decreased Ca2+ loading capacity; altered fission/fusion dynamics; mitochondrial bioenergetic deficits; decreased mtDNA copy number; impaired mitochondrial membrane depolarization | [174,175,176,177] |
Parkinson’s Disease | PARKIN, PINK1, DJ-1, ATP13A2, SNCA, LRRK2 | I, II, IV | Reduced functioning in mitochondrial ETC components; decrease in mitochondrial membrane potential; decreased ATP production; increased ROS production; abnormal mitochondrial morphology; decreased mitochondrial import; decreased mtDNA copy number; increased mitophagy | [33,178,179,180,181] |
Alzheimer’s Disease | APP, PS1, PS2, APOE4 | IV | Reduced functioning in mitochondrial ETC components; abnormal mitochondrial morphology; decreased ATP production; increased ROS production; decreased expression and activation of mitochondrial enzymes; altered fission/fusion dynamics; decreased mitochondrial membrane potential and mtDNA copy number; abnormal mitophagy | [172,182,183,184,185,186,187] |
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Bartman, S.; Coppotelli, G.; Ross, J.M. Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases. Curr. Issues Mol. Biol. 2024, 46, 1987-2026. https://doi.org/10.3390/cimb46030130
Bartman S, Coppotelli G, Ross JM. Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases. Current Issues in Molecular Biology. 2024; 46(3):1987-2026. https://doi.org/10.3390/cimb46030130
Chicago/Turabian StyleBartman, Sydney, Giuseppe Coppotelli, and Jaime M. Ross. 2024. "Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases" Current Issues in Molecular Biology 46, no. 3: 1987-2026. https://doi.org/10.3390/cimb46030130
APA StyleBartman, S., Coppotelli, G., & Ross, J. M. (2024). Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases. Current Issues in Molecular Biology, 46(3), 1987-2026. https://doi.org/10.3390/cimb46030130