The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes

Luo, Jian-Sheng; Ning, Jiaqi; Chen, Zhuo-Ya; Li, Wenjing; Zhou, Ruiling; Yan, Ru-Yu; Chen, Meng-Jie; Ding, Lingling

doi:10.1007/s11064-022-03631-y

Cited by 20 publications

(9 citation statements)

References 188 publications

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“…The similar metabolic lesions of oxidative stress and mitochondrial dysfunction described for DPN, Parkinson's and Alzheimer's diseases, concur with reports of enhanced risk factors for the associations of these neurodegenerative conditions [13] [71] [72]. Malfunctions in redox parameters and apoptosis are also characteristics of tumour cells, and so it is unsurprising to find drugs with efficacy against cancer being applied to neurodegenerative conditions, or to discover that experimental models developed to study different neurodegenerative conditions are responsive to the same compounds.…”

Section: Discussionsupporting

confidence: 84%

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

Williams¹

2023

JBM

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Neurodegeneration is attributable to metabolic disturbances in the various cell types responsible for this condition, in respect of glucose utilisation and dysfunctional mitochondrial oxidative mechanisms. The properties of neurotoxins and antagonists that limit their action are well documented in disease models, whereas effective therapy is very limited. Cell apoptosis, a general marker of neurodegeneration, is also of therapeutic interest in the treatment of cancer. cGMP nucleotide influences apoptosis and has a role in maintaining equilibrium within cell redox parameters. The chemical structure of cGMP provides a comparative template for demonstrating relative molecular similarity within the structures of natural and synthetic compounds influencing tumour cell apoptosis. The present study uses computational software to investigate molecular similarity within the structures of cGMP and compounds that modulate cell apoptosis in experimental models of diabetic peripheral neuropathy (DPN), Parkinson's and multiple sclerosis. Differential molecular similarity demonstrated in neurotoxin and antagonist structures implicate metabolite impairment of cGMP signaling function as a common mechanism in the initial phases of these neurodegenerative conditions.

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Section: Discussionsupporting

confidence: 84%

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

Williams¹

2023

JBM

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“…It can also interact with the pathological products of AD. Defects in mitochondrial quality control, also known as mitochondrial dysfunction could lead to cognitive dysfunction in DM (Ng et al, 2021;Luo et al, 2022). Decreased mitochondrial respiration, disrupted membrane potential, and reduced energy synthesis, which is associated with the progression of AD, cause synaptic injury in diabetic AD mice (Carvalho et al, 2015).…”

Section: Mitochondria Dysfunctionmentioning

confidence: 99%

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Wang

Liu

et al. 2023

Front. Pharmacol.

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Alzheimer’s Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3β and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.

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“…Accumulated oxidative damage causes an altered oxidative phosphorylation and redox imbalance in mitochondria [83]. The long-lasting effect can lead to the des-regulation of mitochondrial protein homeostasis, and consequent proteotoxic stress in the neurons [84]. Neurons in the central nervous system have a high requirement for energy as attributed to their constant activity and signaling, and thus are especially vulnerable to mitochondrial dysfunction.…”

Section: Protect Mitochondria Functionmentioning

confidence: 99%

Cognitive Impairment in Diabetes Mellitus and Its Management by Transcription Factor Nrf2-Mediated Antioxidant Defense System

Zhou¹,

Münch²,

Chang³

2023

Importance of Oxidative Stress and Antioxidant System in Health and Disease

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Diabetes mellitus has been an epidemic in the twenty-first century and an approximately 50% risk of diabetes predisposed to cognitive decline leading to dementia in humans. There is an urgent need to understand the pathophysiology and identify molecular targets of cognitive impairment in diabetes mellitus that might lead to improved therapy. Mounting evidence indicates that nuclear factor erythroid 2-related factor 2 (Nrf2) and its regulated downstream antioxidant genes are emerging therapeutic targets. In this chapter, we introduce cognitive dysfunction in diabetes mellitus and its hallmarks, particularly its pathological mechanisms related to oxidative stress in the brain, then justify the role of the transcription factor Nrf2-mediated antioxidant defense system in attenuating cognitive decline in diabetes mellitus. Studies on Nrf2 inducers sourced from natural products (i.e., sulforaphane, astaxanthin, resveratrol, quercetin) that have shown potent cognitive improvement in diabetic models are discussed. These studies have demonstrated that Nrf2 inducers drive the antioxidant and anti-inflammatory responses in the hippocampus region and effectively improve the spatial and memory function in diabetic rats/mice. However, evidence from large and well-designed clinical trials is warranted to support Nrf2 inducers as promising therapeutic agents in the management of cognitive impairment in diabetes mellitus.

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The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes

Cited by 20 publications

References 188 publications

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

Relative Molecular Similarity in Compound Structures Modulating Neurodegenerative Apoptosis

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Cognitive Impairment in Diabetes Mellitus and Its Management by Transcription Factor Nrf2-Mediated Antioxidant Defense System

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