Mitochondrial dysfunction alters energy metabolism, cellular respiration and plays a major role in the genesis of Alzheimer’s disease (AD). Altered mitochondrial and neuronal health could be considered as early features of AD. Alzheimer’s is characterized by memory loss, cognitive impairment, loss of learning abilities, and pathologically it is characterized by neuronal and synaptic loss, intraneuronal accumulation of neurofibrillary tangles and extraneuronal deposition of amyloid plaques. Mitochondrial dysfunction is attributed to the failure in the regulation of energy metabolism, an imbalance in fission, fusion and mitophagy but not limiting to ROS/oxidative stress. All these events exacerbate mitochondrial damage and enhance the formation process of phosphorylated tangles (PTs) and amyloid plaques but few other investigators claim that formed PTs and amyloid plaques may cause the mitochondrial dysfunction and defective biogenesis. Recent studies have shown that mitochondrial fission and its receptor proteins are also working under the supervision of some key mitophagy proteins. Once the mitophagy action is implemented, autophagy action will be triggered to clear dead mitochondria and other organelles by lysosomes for active function of neurons. Mitophagy, mitochondrial fission and fusion should be orchestrated properly for the active maintenance of mitochondria in continuous supply of energy for the functioning of neurons and Tau and axonal metabolism for neuronal and synaptic plasticity. In addition, due to dysfunctional mitochondria, there is a direct effect on anterograde and retrograde (still under investigation) trafficking and eventually effects neuronal trafficking across the neurons. Intriguingly, abnormal regulation of mitochondrial division protein Drp1 directly causes in forming Tau tangles inside the neurons, also regulates mitophagy proteins such as PINK1, Optineurin, p62, VDAC, NDP52 and their receptors i.e. Nix1, FUNDC1, AMBRA1 etc. These cascade events eventually affect autophagy proteins such as ATG5-12-16, ATG7, and LC3. Mitophagy has been compromised not only in AD but also in other neurodegenerative diseases like Parkinson’s disease and aging. Since decade umpteen literature laminating crosslinks between mitochondrial dysfunction, defective Mitophagy, and Autophagy in Alzheimer’s disease. Emerging studies also suggested that compromised mitophagy and autophagy not only in AD but also in other degenerative diseases. In addition, conditions like diabetes and diseases like cancer, cardiovascular diseases have also shown compromised mitophagy.
This Research Topic seeks contributions focusing on the molecular, cellular, physiological, and neuronal circuit/network mechanisms role in mitochondrial dysfunction (and integrity), mitophagy, and autophagy in causing dementia of Alzheimer’s disease and other neurodegenerative diseases. We also welcome studies focusing on causative factors which affects mitophagy and autophagy from other human diseases, which play pivotal role in influencing these mechanisms and ultimately causing neurodegeneration.
Mitochondrial dysfunction alters energy metabolism, cellular respiration and plays a major role in the genesis of Alzheimer’s disease (AD). Altered mitochondrial and neuronal health could be considered as early features of AD. Alzheimer’s is characterized by memory loss, cognitive impairment, loss of learning abilities, and pathologically it is characterized by neuronal and synaptic loss, intraneuronal accumulation of neurofibrillary tangles and extraneuronal deposition of amyloid plaques. Mitochondrial dysfunction is attributed to the failure in the regulation of energy metabolism, an imbalance in fission, fusion and mitophagy but not limiting to ROS/oxidative stress. All these events exacerbate mitochondrial damage and enhance the formation process of phosphorylated tangles (PTs) and amyloid plaques but few other investigators claim that formed PTs and amyloid plaques may cause the mitochondrial dysfunction and defective biogenesis. Recent studies have shown that mitochondrial fission and its receptor proteins are also working under the supervision of some key mitophagy proteins. Once the mitophagy action is implemented, autophagy action will be triggered to clear dead mitochondria and other organelles by lysosomes for active function of neurons. Mitophagy, mitochondrial fission and fusion should be orchestrated properly for the active maintenance of mitochondria in continuous supply of energy for the functioning of neurons and Tau and axonal metabolism for neuronal and synaptic plasticity. In addition, due to dysfunctional mitochondria, there is a direct effect on anterograde and retrograde (still under investigation) trafficking and eventually effects neuronal trafficking across the neurons. Intriguingly, abnormal regulation of mitochondrial division protein Drp1 directly causes in forming Tau tangles inside the neurons, also regulates mitophagy proteins such as PINK1, Optineurin, p62, VDAC, NDP52 and their receptors i.e. Nix1, FUNDC1, AMBRA1 etc. These cascade events eventually affect autophagy proteins such as ATG5-12-16, ATG7, and LC3. Mitophagy has been compromised not only in AD but also in other neurodegenerative diseases like Parkinson’s disease and aging. Since decade umpteen literature laminating crosslinks between mitochondrial dysfunction, defective Mitophagy, and Autophagy in Alzheimer’s disease. Emerging studies also suggested that compromised mitophagy and autophagy not only in AD but also in other degenerative diseases. In addition, conditions like diabetes and diseases like cancer, cardiovascular diseases have also shown compromised mitophagy.
This Research Topic seeks contributions focusing on the molecular, cellular, physiological, and neuronal circuit/network mechanisms role in mitochondrial dysfunction (and integrity), mitophagy, and autophagy in causing dementia of Alzheimer’s disease and other neurodegenerative diseases. We also welcome studies focusing on causative factors which affects mitophagy and autophagy from other human diseases, which play pivotal role in influencing these mechanisms and ultimately causing neurodegeneration.
