Pathology and Treatments of Alzheimer’s Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes DOI Creative Commons
Hidekatsu Yanai,

Hiroki Adachi,

Mariko Hakoshima

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 5936 - 5936

Published: Dec. 16, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, it pathologically characterized by the accumulation of amyloid plaques neurofibrillary tangles in brain. Although various hypotheses have been proposed to explain pathogenesis AD, including beta hypothesis, oxidative stress abnormal phosphorylation tau proteins, exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited. Epidemiologic studies provide convincing evidence for significant association between type 2 diabetes AD. Here, we showed energy metabolism using glucose, lactate, ketone bodies, lipids as substrates normal brain, changes such due diabetes. We also influences altered on pathology comprehensively searched risk factors related possible therapeutic interventions based considering brain development

Language: Английский

The Interplay of Aging, Sleep Dysregulation, and Mitochondrial Dysfunction in Metabolic and Neurodegenerative Diseases DOI Creative Commons
Kuo-Jen Lin, I‐Hung Shao, Yu‐Hsiang Lin

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107614 - 107614

Published: Jan. 18, 2025

Language: Английский

Citations

2
A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases DOI Creative Commons

Caterina Vicidomini,

Francesco Fontanella, Tiziana D’Alessandro

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1330 - 1330

Published: Oct. 19, 2024

Currently, the age structure of world population is changing due to declining birth rates and increasing life expectancy. As a result, physicians worldwide have treat an number age-related diseases, which neurological disorders represent significant part. In this context, there urgent need discover new therapeutic approaches counteract effects neurodegeneration on human health, computational science can be pivotal importance for more effective neurodrug discovery. The knowledge molecular receptors other biomolecules involved in pathogenesis facilitates design molecules as potential drugs used fight against diseases high social relevance such dementia, Alzheimer's disease (AD) Parkinson's (PD), cite only few. However, absence comprehensive guidelines regarding strengths weaknesses alternative creates fragmented disconnected field, resulting missed opportunities enhance performance achieve successful applications. This review aims summarize some most innovative strategies based methods development. particular, recent applications state-of-the-art docking artificial intelligence ligand- target-based novel drug were reviewed, highlighting crucial role silico context discovery neurodegenerative diseases.

Language: Английский

Citations

6
Metabolic Regulation and Cardiorenal Protection: Deciphering the Potential and Multi-Target Mechanisms of Jiangtang Qingre Formula for Type 2 Diabetes Management DOI
Lijuan Zhou, Jingyi Zhao, Rui Hao

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Age-related hearing loss: the complex interaction of carbohydrate metabolism in auditory and cognitive dysfunction during aging DOI Open Access

Shengyu Zou,

Yue Liu, Bowen Xu

et al.

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: 5(1)

Published: March 31, 2025

Age-related hearing loss (ARHL) is an extremely widespread form of age-related disease mainly characterized by high-frequency and subsequent cognitive dysfunction. The pathological changes associated with ARHL involve both peripheral auditory structures the central nervous system. Recent studies have focused on aging mechanisms sensors, such as cochlear hair cells, spiral ganglion stria vascularis. Additionally, role carbohydrate metabolic signaling pathways in has garnered attention, particularly regulatory effects glycolysis, glycosylation pathway, pentose phosphate pathway. dysfunction a significant clinical symptom advanced stages ARHL, growing evidence suggests that may be closely linked to Alzheimer’s disease, potentially serving risk factor for its development. In this review, we summarize specific regulators metabolism contribute ARHL. Furthermore, discuss recent research progress relationship between metabolism, loss, Finally, explore novel therapeutic targets future prospects understanding pathogenesis diagnosis related aging-associated diseases.

Language: Английский

Citations

0
In Vivo and Computational Studies on Sitagliptin’s Neuroprotective Role in Type 2 Diabetes Mellitus: Implications for Alzheimer’s Disease DOI Creative Commons
Vasudevan Mani, Minhajul Arfeen

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(12), P. 1191 - 1191

Published: Nov. 26, 2024

Background/Objectives: Diabetes mellitus (DM), a widespread endocrine disorder characterized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer’s disease (AD). Effective blood glucose management is essential, sitagliptin (SITG), dipeptidyl peptidase-4 (DPP-4) inhibitor, may offer neuroprotective benefits in type 2 diabetes (T2DM). Methods: T2DM was induced rats using nicotinamide (NICO) streptozotocin (STZ), biomarkers AD DM-linked enzymes, inflammation, oxidative stress, apoptosis were evaluated brain. Computational studies supported vivo findings. Results: SITG significantly reduced brain enzyme levels acetylcholinesterase (AChE), beta-secretase-1 (BACE-1), DPP-4, glycogen synthase kinase-3β (GSK-3β) T2DM-induced rats. It also inflammation lowering cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB). Additionally, improved stress markers reducing malondialdehyde (MDA) enhancing glutathione (GSH). increased anti-apoptotic B-cell lymphoma protein-2 (Bcl-2) while pro-apoptotic Bcl-2-associated X (BAX) Caspace-3. lowered plasma insulin levels. To explore potential molecular level mechanisms, docking performed on AChE, COX-2, GSK-3β, BACE-1, The binding affinity for above-mentioned target enzymes 10.8, 8.0, 9.7, 7.7, 7.9 kcal/mol, respectively, comparable to co-crystallized ligands. Further mode analysis lowest energy conformation revealed interactions with critical residues. Conclusions: These findings highlight SITG’s targets T2DM-associated neurodegeneration its therapeutic approach AD, warranting further clinical investigations.

Language: Английский

Citations

3
Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models) DOI Creative Commons
A. Tolédano, Arantxa Rodríguez‐Casado,

María‐Isabel Álvarez

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(11), P. 1101 - 1101

Published: Oct. 30, 2024

Obesity, type 2 diabetes (T2D), and Alzheimer's disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy difficult to prevent control when they develop. It has been known for many years these diseases pathogenic aspects in common. We highlight this review neuroglial cells (astroglia, oligodendroglia, microglia) play a vital role the origin, clinical-pathological development, course brain neurodegeneration. Moreover, we include new results T2D-AD mouse model (APP+PS1 mice on high-calorie diet) investigating.

Language: Английский

Citations

3
Pathology and Treatments of Alzheimer’s Disease Based on Considering Changes in Brain Energy Metabolism Due to Type 2 Diabetes DOI Creative Commons
Hidekatsu Yanai,

Hiroki Adachi,

Mariko Hakoshima

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 5936 - 5936

Published: Dec. 16, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction, memory decline, and behavioral disturbance, it pathologically characterized by the accumulation of amyloid plaques neurofibrillary tangles in brain. Although various hypotheses have been proposed to explain pathogenesis AD, including beta hypothesis, oxidative stress abnormal phosphorylation tau proteins, exact pathogenic mechanisms underlying AD remain largely undefined. Furthermore, effective curative treatments are very limited. Epidemiologic studies provide convincing evidence for significant association between type 2 diabetes AD. Here, we showed energy metabolism using glucose, lactate, ketone bodies, lipids as substrates normal brain, changes such due diabetes. We also influences altered on pathology comprehensively searched risk factors related possible therapeutic interventions based considering brain development

Language: Английский

Citations

1