Targeting Glucose Metabolism: A Novel Therapeutic Approach for Parkinson’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1876 - 1876

Published: Nov. 13, 2024

Glucose metabolism is essential for the maintenance and function of central nervous system. Although brain constitutes only 2% body weight, it consumes approximately 20% body’s total energy, predominantly derived from glucose. This high energy demand underscores its reliance on glucose to fuel various functions, including neuronal activity, synaptic transmission, ion gradients necessary nerve impulse transmission. Increasing evidence shows that many neurodegenerative diseases, Parkinson’s disease (PD), are associated with abnormalities in metabolism. PD characterized by progressive loss dopaminergic neurons substantia nigra, accompanied accumulation α-synuclein protein aggregates. These pathological features exacerbated mitochondrial dysfunction, oxidative stress, neuroinflammation, all which influenced disruptions. Emerging suggests targeting could offer therapeutic benefits PD. Several antidiabetic drugs have shown promise animal models clinical trials mitigating symptoms progression review explores current understanding association between metabolism, emphasizing potential medications as a novel approach. By improving uptake utilization, enhancing function, reducing these address key pathophysiological mechanisms PD, offering hope more effective management this debilitating disease.

Language: Английский

---

Genome-Wide Mapping Implicates 5-Hydroxymethylcytosines in Diabetes Mellitus and Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 93(3), P. 1135 - 1151

Published: May 10, 2023

Diabetes mellitus (DM) is a recognized risk factor for dementia. Because DM potentially modifiable condition, greater understanding of the mechanisms linking to clinical expression Alzheimer's disease dementia may provide insights into much needed therapeutics.In this feasibility study, we investigated as by examining genome-wide distributions epigenetic DNA modification 5-hydroxymethylcytosine (5hmC).We obtained biologic samples from Rush Memory and Aging Project used highly sensitive 5hmC-Seal technique perform profiling 5hmC in circulating cell-free (cfDNA) antemortem serum genomic postmortem prefrontal cortex brain tissue 80 individuals across four groups: neuropathologically defined (AD), clinically defined, AD with DM, neither (controls).Distinct signatures biological pathways were enriched persons both versus alone, or controls, including genes inhibited EGFR signaling oligodendroglia those activated constitutive RHOA. We also demonstrate potential diagnostic value cfDNA. Specifically, an 11-gene weighted model distinguished non-AD/non-DM controls (AUC = 91.8%; 95% CI, 82.9-100.0%), while 4-gene DM-associated alone 87.9%; 77.5-98.3%).We small sample, detecting characterizing using information contained cfDNA detect high-risk individuals, such diabetes.

Language: Английский

---

Neuroregeneration Improved by Sodium-D,L-Beta-Hydroxybutyrate in Primary Neuronal Cultures

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1160 - 1160

Published: Aug. 31, 2024

Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, density and degree regeneration in damaged areas (gaps) absence (control) presence BHB (2 mM) documented with automated live-cell imaging by CytoSMART over 24 h, which was followed immunocytochemistry, labeling synapsin-I β3-tubulin. significantly higher gaps treatment after h compared control. In control, only 1.5% measured gap became narrower while BHB-treated samples 49.23% h. expanded 63.81% post-injury, size decreased 10.83% response treatment, baseline. increased 97.27% reduced 74.64% BHB, distance travelled velocity migrating cells more β3-tubulin found results demonstrate that D/L-BHB enhanced migration molecular processes associated neural axonogenesis. These may have clinical therapeutic applications future injuries, such as stroke, concussion TBI patients.

Language: Английский

---

From Plaques to Pathways in Alzheimer’s Disease: The Mitochondrial-Neurovascular-Metabolic Hypothesis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11720 - 11720

Published: Oct. 31, 2024

Alzheimer's disease (AD) presents a public health challenge due to its progressive neurodegeneration, cognitive decline, and memory loss. The amyloid cascade hypothesis, which postulates that the accumulation of amyloid-beta (Aβ) peptides initiates leading AD, has dominated research therapeutic strategies. failure recent Aβ-targeted therapies yield conclusive benefits necessitates further exploration AD pathology. This review proposes Mitochondrial-Neurovascular-Metabolic (MNM) integrates mitochondrial dysfunction, impaired neurovascular regulation, systemic metabolic disturbances as interrelated contributors pathogenesis. Mitochondrial hallmark leads oxidative stress bioenergetic failure. Concurrently, breakdown blood-brain barrier (BBB) cerebral blood flow, characterize dysregulation, accelerate neurodegeneration. Metabolic such glucose hypometabolism insulin resistance impair neuronal function survival. hypothesis highlights interconnectedness these pathways suggests strategies targeting health, integrity, regulation may offer more effective interventions. MNM addresses multifaceted aspects providing comprehensive framework for understanding progression developing novel approaches. approach paves way innovative could significantly improve outcomes millions affected worldwide.

Language: Английский

---

Interplay of Angiotensin Peptides, Vasopressin, and Insulin in the Heart: Experimental and Clinical Evidence of Altered Interactions in Obesity and Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1310 - 1310

Published: Jan. 21, 2024

The present review draws attention to the specific role of angiotensin peptides [angiotensin II (Ang II), angiotensin-(1-7) (Ang-(1-7)], vasopressin (AVP), and insulin in regulation coronary blood flow cardiac contractions. interactions peptides, AVP, heart brain are also discussed. intracardiac production supply AVP from systemic circulation enable their easy access vessels cardiomyocytes. Coronary cardiomyocytes furnished with AT1 receptors, AT2 Ang (1-7) V1 receptor substrates. presence some these molecules same cells creates good conditions for interaction at signaling level. broad spectrum actions allows engagement most vital processes, including (1) tissue oxygenation, energy production, metabolism; (2) generation other cardiovascular compounds, such as nitric oxide, bradykinin (Bk), endothelin; (3) work by autonomic nervous system neurons brain. Multiple experimental studies clinical observations show that II, Ang(1-7), markedly altered during failure, hypertension, obesity, diabetes mellitus, especially when diseases coexist. A survey literature presented provides evidence belief very individualized treatment, angiotensins insulin, should be applied patients suffering both metabolic diseases.

Language: Английский

---