Abstract
Lead (Pb) is a multimedia contaminant with various pathophysiological consequences, including cognitive decline and neural abnormalities. Recent findings have reported an association of Pb toxicity with Alzheimer’s disease (AD). Studies have revealed that mitochondrial dysfunction is a pathological characteristic of AD. According to toxicology reports, Pb promotes mitochondrial oxidative stress by lowering complex III activity in the electron transport chain, boosting reactive oxygen species formation, and reducing the cell’s antioxidant defence system. Here, we review recent advances in the role of mitochondria in Pb-induced AD pathology, as well as the mechanisms associated with the mitochondrial dysfunction, such as the depolarisation of the mitochondrial membrane potential, mitochondrial permeability transition pore opening; mitochondrial biogenesis, bioenergetics and mitochondrial dynamics alterations; and mitophagy and apoptosis. We also discuss possible therapeutic options for mitochondrial-targeted neurodegenerative disease (AD).
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Abbreviations
- Pb:
-
Lead
- AD:
-
Alzheimer’s disease
- NFT:
-
Neurofibrillary tangles
- Aβ:
-
Amyloid-beta
- APP:
-
Amyloid precursor protein
- BACE1:
-
Beta-secretase
- NMDA:
-
N-methyl d-aspartic acid
- ROS:
-
Reactive oxygen species
- ETC:
-
Electron transport chain
- TCA:
-
Tricarboxylic acid cycle
- MMP:
-
Mitochondrial membrane potential
- MPTP:
-
Mitochondrial permeability transition pore
- TOM:
-
Translocase of outer mitochondrial membrane
- VDAC:
-
Voltage-dependent anion channel
- Mt DNA:
-
Mitochondrial DNA
- PGC-1α:
-
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
- NRF:
-
Nuclear respiratory factors
- TFAM:
-
Mitochondrial transcription factor A
- SIRT3:
-
Sirtuin3
- OPA1:
-
Optic atrophy factor 1
- Mfn:
-
Mitofusin
- Drp1:
-
Dynamin related protein-1
- Fis1:
-
Fission protein 1
- Mff:
-
Mitochondrial fission factor
- MIRO:
-
Mitochondrial Rho small GTPase
- KLC:
-
Kinesin light chain
- DIC:
-
Dynein intermediate chain
- PINK1:
-
PTEN-induced putative kinase protein1
- CypD:
-
Cyclophilin D
- ANT:
-
Adenine nucleotide translocase
- AIF:
-
Apoptosis-inducing factor
- SOD:
-
Superoxide dismutase
- GSH-Px:
-
Glutathione peroxidase
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Acknowledgements
We thank the Indian Council of Medical Research (ICMR) for providing funds to carryout research and the University grants commission (UGC), Govt. of India for the award of the fellowship.
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This work has been supported by the Grant 58/57/2012-BMS funded by Indian Council of Medical Research (ICMR).
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Bandaru, L.J.M., Ayyalasomayajula, N., Murumulla, L. et al. Mechanisms associated with the dysregulation of mitochondrial function due to lead exposure and possible implications on the development of Alzheimer’s disease. Biometals 35, 1–25 (2022). https://doi.org/10.1007/s10534-021-00360-7
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DOI: https://doi.org/10.1007/s10534-021-00360-7