Antidiabetic agents as a novel treatment for Alzheimer’s and Parkinson’s disease

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101979 - 101979

Published: June 15, 2023

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's (PD), are characterized by several pathological features. In AD PD, there is an abnormal accumulation toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, astrocyte activation, perhaps a state insulin resistance. Epidemiological evidence has revealed link between AD/PD type 2 diabetes mellitus, with these sharing some commonalities. Such opened up promising avenue repurposing antidiabetic agents in treatment disorders. A successful therapeutic strategy would likely require single or which target separate processes disease. Targeting cerebral signalling produces numerous neuroprotective effects preclinical brain models. Clinical trials shown promise approved diabetic compounds improving motor symptoms PD preventing decline, further phase II III underway populations. Alongside signalling, targeting incretin receptors represents one most currently available AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists displayed impressive clinical potential early studies. GLP-1 agonist, liraglutide, been demonstrated improve glucose metabolism functional connectivity small-scale pilot trials. Whilst agonist exenatide effective restoring function cognition. reduces inhibits apoptosis, prevents protein aggregation, enhances long-term potentiation autophagy as well restores dysfunctional signalling. Support also increasing use additional treatments, intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear γ agonists, amylin analogs, tyrosine phosphatase 1B inhibitors investigation deployment treatment. As such, we provide comprehensive review anti-diabetic PD.

Language: Английский

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New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases

Aging and Disease, Journal Year: 2021, Volume and Issue: 12(8), P. 1948 - 1948

Published: Jan. 1, 2021

High incidences of morbidity and mortality associated with age-related diseases among the elderly population are a socio-economic challenge. Aging is an irreversible inevitable process that risk factor for pathological progression diverse diseases. Spermidine, natural polyamine, plays critical role in molecular cellular interactions involved various physiological functional processes. Spermidine has been shown to modulate aging, suppress occurrence severity diseases, prolong lifespan. However, precise mechanisms through which spermidine exerts its anti-aging effects have not established. In this review, we elucidate on roles underlying beneficial aging from perspective. Moreover, provide new insights into promising potential diagnostic therapeutic applications

Language: Английский

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Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 4, 2022

Abstract Inflammation is the common pathological basis of autoimmune diseases, metabolic malignant tumors, and other major chronic diseases. plays an important role in tissue homeostasis. On one hand, inflammation can sense changes environment, induce imbalance homeostasis, cause damage. also initiate damage repair maintain normal function by resolving injury restoring These opposing functions emphasize significance accurate regulation inflammatory homeostasis to ameliorate inflammation-related Potential mechanisms involve protein phosphorylation modifications kinases phosphatases, which have a crucial The many resolve been well reviewed, whereas systematic summary phosphatases regulating lacking. molecular knowledge especially unique biochemical traits each family member, will be critical importance for developing drugs that target phosphatases. Here, we provide comprehensive structure, “double-edged sword” function, extensive signaling pathways all as their potential inhibitors or activators used therapeutic interventions preclinical clinical trials. We integrated perspective on current understanding associated with aim facilitating development treatment

Language: Английский

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Therapeutic Application of Lantibiotics and Other Lanthipeptides: Old and New Findings

Applied and Environmental Microbiology, Journal Year: 2021, Volume and Issue: 87(14)

Published: May 7, 2021

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, with modifications that incorporated during biosynthesis by dedicated enzymes. Various of the peptides possible, resulting in a highly diverse group bioactive offer potential reservoir for use fight against plethora diseases.

Language: Английский

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Dexmedetomidine Provides Protection Against Hippocampal Neuron Apoptosis and Cognitive Impairment in Mice with Alzheimer’s Disease by Mediating the miR-129/YAP1/JAG1 Axis

Molecular Neurobiology, Journal Year: 2020, Volume and Issue: 57(12), P. 5044 - 5055

Published: Aug. 24, 2020

Language: Английский

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Squalamine and trodusquemine: two natural products for neurodegenerative diseases, from physical chemistry to the clinic

Natural Product Reports, Journal Year: 2021, Volume and Issue: 39(4), P. 742 - 753

Published: Oct. 26, 2021

The natural products squalamine and trodusquemine are promising potential therapeutics against Alzheimer's, Parkinson's, other neurodegenerative diseases for their ability to modulate protein aggregation processes target misfolded oligomers that toxic neurons.

Language: Английский

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Interorganelle communication, aging, and neurodegeneration

Genes & Development, Journal Year: 2021, Volume and Issue: 35(7-8), P. 449 - 469

Published: April 1, 2021

Our cells are comprised of billions proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather interconnected hubs engage in extensive communication through membrane contacts. In last few years, our understanding how these contacts coordinate organelle function has redefined view cell. This review aims to present novel findings on interorganelle network its dysfunction may contribute aging neurodegeneration. The consequences disturbed interorganellar intimately linked age-related pathologies. Given both neurodegenerative diseases characterized by concomitant failure multiple pathways, coordination could represent an emerging regulatory mechanism critical for long-term homeostasis. We anticipate defining relationships between communication, aging, neurodegeneration will open new avenues therapeutics.

Language: Английский

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Protein tyrosine phosphatase 1B (PTP1B) as a potential therapeutic target for neurological disorders

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113709 - 113709

Published: Sept. 19, 2022

Protein tyrosine phosphatase 1B (PTP1B) is a typical member of the PTP family, considered direct negative regulator several receptor and receptor-associated kinases. This widely localized enzyme has been involved in pathophysiology diseases. More recently, PTP1B attracted attention field neuroscience, since its activation brain cells can lead to schizophrenia-like behaviour deficits, anxiety-like effects, neurodegeneration, neuroinflammation depression. Conversely, inhibition shown prevent microglial activation, thus exerting potent anti-inflammatory effect also potential increase cognitive process through stimulation hippocampal insulin, leptin BDNF/TrkB receptors. Notwithstanding, most research on clinical efficacy targeting developed obesity type 2 diabetes mellitus (TD2M). However, despite link existing between these metabolic alterations no trials assessing neurological advantages have performed yet. Preclinical studies, though, provided strong evidence that could allow reach different pathophysiological mechanisms at once. herefore, specific interventions or should be designed modulate activity brain, it promising strategy decelerate neurodegeneration aged individuals, among other The present paper fails include all conditions which role; instead, focuses those related neurodegenerative processes. Moreover, only preclinical data discussed, studies for treating diseases are still required.

Language: Английский

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Protein Tyrosine Phosphatase 1B (PTP1B): A Comprehensive Review of Its Role in Pathogenesis of Human Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7033 - 7033

Published: June 27, 2024

Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented the pathogenesis metabolic disorders (diabetes mellitus type I II, fatty liver disease, obesity); neurodegenerative diseases (Alzheimer's Parkinson's disease); major depressive disorder; calcific aortic valve disease; as several cancer types. Given this multitude therapeutic applications, shortly after identification PTP1B role, pursuit to introduce safe selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed failed, or are yet complete, clinical trials. Intending aid introduction new generation inhibitors, work collects organizes current state art. review intends elucidate intricate relations between associated with overexpression PTP1B, we believe that it is utmost significance establish follow a brand-new holistic approach treatment interconnected conditions. With mind, comprehensive aims validate promising molecular target, reinforce future research direction.

Language: Английский

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True or false? Alzheimer’s disease is type 3 diabetes: Evidences from bench to bedside

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102383 - 102383

Published: June 30, 2024

Globally, Alzheimer's disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, well mental symptoms, like behavioral abnormalities, that place a heavy psychological financial burden on families of afflicted. Unfortunately, no particular medications exist treat AD, current treatments only impede its progression.The link between AD type 2 diabetes (T2D) has been increasingly revealed by research; danger developing both T2D rises exponentially with age, being especially prone AD. This propelled researchers investigate mechanism(s) underlying this connection. A critical review relationship insulin resistance, Aβ, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation Tau protein, inflammatory response, high blood glucose levels, neurotransmitters signaling pathways, vascular issues in diabetes, similarities two diseases, presented review. Grasping essential mechanisms behind detrimental interaction may offer chances devise successful therapeutic strategies.

Language: Английский

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