Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress

Dewanjee, Saikat; Chakraborthy, Pratik; Bhattacharya, Hiranmoy; Chacko, Leena; Singh, Bhoj Raj; Chaudhary, Anupama; Javvaji, Kalpana; Pradhan, Saumya Ranjan; Vallamkondu, Jayalakshmi; Dey, Abhijit; Kalra, Rajkumar S.; Jha, Niraj Kumar; Jha, Saurabh; Reddy, P. Hemachandra; Kandimalla, Ramesh

doi:10.1016/j.freeradbiomed.2022.09.032

Cited by 78 publications

(61 citation statements)

References 397 publications

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“…The administration of the Rock2 inhibitor, fasudil, prevented these pathological events (Bobo-Jimenez et al, 2017), confirming that the APC/CCdh1-Rock2 pathway regulates dendritic network integrity and brain functioning. APC/C-Cdh1 constantly prevent neuronal cycle activation, mitochondrial dysfunction, oxidative stress, and synapse loss, all involved in the pathophysiology of neurodegenerative diseases, and particularly in AD (Dewanjee et al, 2022). This posits APC/ C-Cdh1 targets in the pathogenesis of neurodegeneration.…”

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

“…In neurons, active APC/C-Cdh1 constantly prevents the accumulation of neurotoxic targets involved in cell cycle regulation, metabolism and redox homeostasis, and neuronal plasticity. Interestingly, dysregulation of these processes results in neurodegeneration, linking APC/C-Cdh1 targets to neurodegenerative diseases and particularly to AD ( Dewanjee et al, 2022 ).…”

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

“…Impaired mitochondrial dysfunction and oxidative stress are characteristic features of AD involved in brain damage and cognitive decline ( Dewanjee et al, 2022 ). Besides of cyclin B1, the accumulation of other APC/C-Cdh1 targets also promote mitochondrial damage and oxidative stress, which potentiate neurodegeneration.…”

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

“…APC/C-Cdh1 constantly prevent neuronal cycle activation, mitochondrial dysfunction, oxidative stress, and synapse loss, all involved in the pathophysiology of neurodegenerative diseases, and particularly in AD ( Dewanjee et al, 2022 ). This posits APC/C-Cdh1 targets in the pathogenesis of neurodegeneration.…”

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

“…Under excitotoxic conditions, the accumulation of APC/C-Cdh1 targets would potentiate neurodegeneration by modulating different and complementary signalling pathways involving mitochondrial function ( Figure 2 ). Furthermore, mitochondrial energy generation is necessary for neuroplasticity ( Dewanjee et al, 2022 ). Therefore, APC/C-Cdh1 targets are interconnected and involved in neurodegeneration, then representing useful tools to develop new treatments for neurodegenerative diseases.…”

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

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APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer’s disease

Lapresa

Agulla²,

Bolaños³

et al. 2022

Front. Pharmacol.

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the main cause of dementia in the elderly. The disease has a high impact on individuals and their families and represents a growing public health and socio-economic burden. Despite this, there is no effective treatment options to cure or modify the disease progression, highlighting the need to identify new therapeutic targets. Synapse dysfunction and loss are early pathological features of Alzheimer’s disease, correlate with cognitive decline and proceed with neuronal death. In the last years, the E3 ubiquitin ligase anaphase promoting complex/cyclosome (APC/C) has emerged as a key regulator of synaptic plasticity and neuronal survival. To this end, the ligase binds Cdh1, its main activator in the brain. However, inactivation of the anaphase promoting complex/cyclosome-Cdh1 complex triggers dendrite disruption, synapse loss and neurodegeneration, leading to memory and learning impairment. Interestingly, oligomerized amyloid-β (Aβ) peptide, which is involved in Alzheimer’s disease onset and progression, induces Cdh1 phosphorylation leading to anaphase promoting complex/cyclosome-Cdh1 complex disassembly and inactivation. This causes the aberrant accumulation of several anaphase promoting complex/cyclosome-Cdh1 targets in the damaged areas of Alzheimer’s disease brains, including Rock2 and Cyclin B1. Here we review the function of anaphase promoting complex/cyclosome-Cdh1 dysregulation in the pathogenesis of Alzheimer’s disease, paying particular attention in the neurotoxicity induced by its molecular targets. Understanding the role of anaphase promoting complex/cyclosome-Cdh1-targeted substrates in Alzheimer’s disease may be useful in the development of new effective disease-modifying treatments for this neurological disorder.

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Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

Section: Apc/c-cdh1 Function In Neurodegenerationmentioning

confidence: 99%

See 3 more Smart Citations

APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer’s disease

Lapresa

Agulla²,

Bolaños³

et al. 2022

Front. Pharmacol.

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Targeted Nano-based Drug Delivery in Alzheimer's Disease and Dementia

Payel Mal,

Rath,

Halder

2024

Smart Nanomaterials Technology

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Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon

Ali,

Al-Kuraishy,

Al-Gareeb

et al. 2024

Cell Mol Neurobiol

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Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory impairment and cognitive dysfunctions. It has been shown that hypoglycemia can adversely affect AD neuropathology. It is well-known that chronic hyperglycemia in type 2 diabetes (T2D) is regarded as a potential risk factor for the development and progression of AD. However, the effect of recurrent hypoglycemia on the pathogenesis of AD was not deeply discussed, and how recurrent hypoglycemia affects AD at cellular and molecular levels was not intensely interpreted by the previous studies. The underlying mechanisms for hypoglycaemia-induced AD are diverse such as endothelial dysfunction, thrombosis, and neuronal injury that causing tau protein hyperphosphorylation and the accumulation of amyloid beta (Aβ) in the brain neurons. Of note, the glucagon hormone, which controls blood glucose, can also regulate the cognitive functions. Glucagon increases blood glucose by antagonizing the metabolic effect of insulin. Therefore, glucagon, through attenuation of hypoglycemia, may prevent AD neuropathology. Glucagon/GLP-1 has been shown to promote synaptogenesis, hippocampal synaptic plasticity, and learning and memory, while attenuating amyloid and tau pathologies. Therefore, activation of glucagon receptors in the brain may reduce AD neuropathology. A recent glucagon receptor agonist dasiglucagon which used in the management of hypoglycemia may be effective in preventing hypoglycemia and AD neuropathology. This review aims to discuss the potential role of dasiglucagon in treating hypoglycemia in AD, and how this drug reduce AD neuropathology.

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Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress

Cited by 78 publications

References 397 publications

APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer’s disease

APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer’s disease

Targeted Nano-based Drug Delivery in Alzheimer's Disease and Dementia

Hypoglycemia and Alzheimer Disease Risk: The Possible Role of Dasiglucagon

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