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 99 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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Redox Oxygen Species‐Responsive Nanotheranostics with Dual‐Channel Fluorescent Turn‐On for Early Diagnosis and Targeted Therapy of Alzheimer's Disease

Guo,

Wang,

Qian

et al. 2024

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Current diagnosis and treatment strategies mainly focus on the pathologies of the mid‐to‐late stage of AD (Alzheimer's disease), with clinical outcomes that are far from ideal. Herein, we developed the ROS (reactive oxygen species)‐responsive brain neuronal targeting nanotheranostic platforms that possess the dual‐channel fluorescent “turn‐on” properties and release drugs in AD neurons in response to ROS, thereby simultaneously facilitating the diagnosis and therapy of early AD. Through the modification of acetylcholine receptor targeting RVG29 peptide, the nanotheranostics penetrated BBB and accumulated into diseased neurons in an intact form, consequently maximizing the diagnostic and therapeutic performance. The anti‐oxidative drug baicalein conjugated onto the surface of nanotheranostics via ROS‐cleavable boronate ester linkage rapidly released for ROS scavenging, while the encapsulated fluorophores turned on their fluorescence for AD diagnosis upon microenvironment stimuli. This nanotheranostic strategy exhibited highly sensitivity with a ROS detection limit of up to 100 µm and accurately early detection of ROS in 3×Tg AD mice at 6 months of age in vivo. In addition, it could also rescue memory defects, scavenge oxidative stress, attenuate neuroinflammation and enhance neuroprotective effect in 3×Tg AD mice. This work opens up a promising and smart strategy for early diagnosis and therapy in neurodegenerative disease.

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