Contributive Role of Hyperglycemia and Hypoglycemia Towards the Development of Alzheimer’s Disease

Chakrabarty, Riya; Yousuf, Sumaira; Singh, Mahendra P.

doi:10.1007/s12035-022-02846-y

Cited by 9 publications

(8 citation statements)

References 158 publications

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“…Protein misfolding appears to occur in AD, resulting in an accumulation of abnormally folded tau-proteins and beta-amyloid in the neurons. A transmembrane protein called amyloid-precursor protein (APP) is essential for the growth of neurons, survival, and repair (post-injury) under optimum conditions [ 39 ]. However, in AD, enzymes break APP into a tiny peptide called A, which are 38-44 amino acids long.…”

Section: Neurodegeneration and Associated Diseasesmentioning

confidence: 99%

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Singh

Chakrabarty

Shabir

et al. 2022

Mediators of Inflammation

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Neurodegenerative disorders are marked by neuronal death over time, causing a variety of cognitive and motor dysfunctions. Protein misfolding, neuroinflammation, and mitochondrial and protein clearance system dysfunction have all been identified as common pathways leading to neurodegeneration in recent decades. An altered microbiome of the gut, which is considered to play a central role in diseases as well as health, has recently been identified as another potential feature seen in neurodegenerative disorders. An array of microbial molecules that are released in the digestive tract may mediate gut-brain connections and permeate many organ systems, including the nervous system. Furthermore, recent findings from clinical as well as preclinical trials suggest that the microbiota of the gut plays a critical part in gut-brain interplay and that a misbalance in the composition of the gut microbiome may be linked to the etiology of neurological disorders (majorly neurodegenerative health problems); the underlying mechanism of which is still unknown. The review aims to consider the association between the microbiota of the gut and neurodegenerative disorders, as well as to add to our understanding of the significance of the gut microbiome in neurodegeneration and the mechanisms that underlie it. Knowing the mechanisms behind the gut microbiome’s role and abundance will provide us with new insights that could lead to novel therapeutic strategies.

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Section: Neurodegeneration and Associated Diseasesmentioning

confidence: 99%

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Singh

Chakrabarty

Shabir

et al. 2022

Mediators of Inflammation

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“…According to epidemiological studies, higher intakes of antioxidant-rich vegetables, fruits, and medicinal herbs are linked with a decreased risk of chronic diseases. Since the high level of free radical production affects apoptosis, cell proliferation, and ion transport, it damages lipids, polypeptides, and DNA and contributes to diseases, including hepatotoxicity [ 6 ], cardiovascular disease, carcinogenesis, and neurological disorders [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells

Yousuf

Shabir²,

Kauts³

et al. 2022

Molecules

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Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

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“…Although physiological blood glucose levels are tightly controlled by endocrine responses, rapid changes in blood glucose, such as hypoglycemia or hyperglycemia in intra-day and inter-day blood glucose variability, can occur. Hyperglycemia produces free radicals and impairs the endogenous antioxidant defense system [ 39 ]. Abnormal metabolism of glucose leads to a glycation reaction, producing advanced glycation end products.…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer’s disease (AD) is one of the most common dementias, and a high prevalence of impaired glucose tolerance or type 2 diabetes has been reported in AD patients [ 39 ]. Amyloid precursor protein (APP) is not only the source of amyloid-β (Aβ) peptides but also directly affects insulin and glucose regulation [ 40 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

Unno

Taguchi

Takagi³

et al. 2023

IJMS

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The sodium–glucose cotransporter 2 (SGLT2) mainly carries out glucose reabsorption in the kidney. Familial renal glycosuria, which is a mutation of SGLT2, is known to excrete glucose in the urine, but blood glucose levels are almost normal. Therefore, SGLT2 inhibitors are attracting attention as a new therapeutic drug for diabetes, which is increasing worldwide. In fact, SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases. However, whether long-term SGLT2 inhibition is completely harmless requires further investigation. In this context, mice with mutations in SGLT2 have been generated and detailed studies are being conducted, e.g., the SGLT2−/− mouse, Sweet Pee mouse, Jimbee mouse, and SAMP10-ΔSglt2 mouse. Biological changes associated with SGLT2 mutations have been reported in these model mice, suggesting that SGLT2 is not only responsible for sugar reabsorption but is also related to other functions, such as bone metabolism, longevity, and cognitive functions. In this review, we present the characteristics of these mutant mice. Moreover, because the relationship between diabetes and Alzheimer’s disease has been discussed, we examined the relationship between changes in glucose homeostasis and the amyloid precursor protein in SGLT2 mutant mice.

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Contributive Role of Hyperglycemia and Hypoglycemia Towards the Development of Alzheimer’s Disease

Cited by 9 publications

References 158 publications

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Influence of the Gut Microbiota on the Development of Neurodegenerative Diseases

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells

Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

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