A Comprehensive Approach to Parkinson’s Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7183 - 7183

Published: June 29, 2024

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by slow progression and varied symptoms. It second most common disease, over six million people in world. Its multifactorial etiology includes environmental, genomic, epigenetic factors. Clinical symptoms consist of non-motor motor symptoms, with being classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, surgical interventions. Traditional pharmacological treatment consists administering drugs (MAOIs, DA, levodopa), while emerging evidence explores potential antidiabetic agents for neuroprotection gene therapy attenuating parkinsonian Non-pharmacological treatments, such as exercise, calcium-rich diet, adequate vitamin D supplementation, aim to prevent complications. For those patients who have medically induced side effects and/or refractory surgery therapeutic option. Deep brain stimulation primary option, associated symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy portable pump succeeded reducing "off" time, where occur, increasing "on" time. This article aims address general aspects PD provide comparative comprehensive review conventional latest advancements treatments PD. Nevertheless, further studies are required optimize suitable alternatives.

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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The growing range of complications of diabetes mellitus

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 115 - 115

Published: Jan. 7, 2025

Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery quality of life. As the aging population grows, rising number patients has made PND an urgent clinical challenge. Despite increasing research efforts, pathophysiological mechanisms underlying remain inadequately characterized, underscoring need for more integrated framework to guide targeted interventions. To better understand molecular therapeutic targets PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches PubMed, Embase, Cochrane Library, Web Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, white matter lesions as central pathophysiology, with particular parallels encephalocele- sepsis-associated impairments. Among these, mediated pathways such NLRP3 inflammasome blood-brain barrier disruption, emerges pivotal driver, triggering cascades exacerbate neuronal injury. Oxidative stress synergistically amplify these effects, while imbalances alterations, including lesions, contribute synaptic decline. Anesthetic agents modulate interconnected pathways, exhibiting both protective detrimental effects. Propofol dexmedetomidine demonstrate neuroprotective properties suppressing neuroinflammation microglial activation, whereas inhalational anesthetics like sevoflurane intensify inflammatory responses. Ketamine, its anti-inflammatory potential, offers promise but requires further evaluation determine long-term safety efficacy. By bridging insights practice, highlights critical role personalized anesthetic strategies mitigating improving patients. It aims inform future decision-making address multifaceted

Language: Английский

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Blood–Brain Barrier Dysfunction and Astrocyte Senescence as Reciprocal Drivers of Neuropathology in Aging

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6217 - 6217

Published: June 1, 2022

As the most abundant cell types in brain, astrocytes form a tissue-wide signaling network that is responsible for maintaining brain homeostasis and regulating various activities. Here, we review some of essential functions perform supporting neurons, modulating immune response, blood-brain barrier (BBB). Given their importance health, it follows astrocyte dysfunction has detrimental effects. Indeed, dysfunctional are implicated age-related neuropathology participate onset progression neurodegenerative diseases. two mechanisms by which mediate aging brain. First, age-associated (BBBD) causes hyperactivation TGFβ astrocytes, elicits pro-inflammatory epileptogenic phenotype. Over time, BBBD-associated results hippocampal cortical neural hyperexcitability cognitive deficits. Second, senescent accumulate with age exhibit decreased functional capacity secretion senescent-associated secretory phenotype (SASP) factors, contribute to neuroinflammation neurotoxicity. Both BBBD senescence progressively increase during associated increased risk disease, but relationship between not yet been established. Thus, discuss potential BBBD, hyperactivation, respect context disease identify future areas investigation field.

Language: Английский

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NF-κB, a culprit of both inflamm-ageing and declining immunity?

Immunity & Ageing, Journal Year: 2022, Volume and Issue: 19(1)

Published: May 17, 2022

NF-κB is generally recognized as an important regulator of ageing, through its roles in cellular senescence and inflammatory pathways. Activated virtually all cell-cell communication networks the immune system, thought to affect age-related defects both innate adaptive cells, relevant inflamm-ageing declining immunity, respectively. Moreover, family proteins that exist heterodimers homodimers exert their function beyond system. Given involvement diverse areas such DNA damage metabolism, has potential serve linkages between known hallmarks ageing. However, complexity dimer composition, dynamic signaling, tissue-specific actions received relatively little attention ageing research. Here, we discuss some where further research may bear fruit our understanding impact healthy longevity.

Language: Английский

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Neurovascular unit dysfunction as a mechanism of seizures and epilepsy during aging

Epilepsia, Journal Year: 2022, Volume and Issue: 63(6), P. 1297 - 1313

Published: Feb. 25, 2022

The term neurovascular unit (NVU) describes the structural and functional liaison between specialized brain endothelium, glial mural cells, neurons. Within NVU, blood-brain barrier (BBB) is microvascular structure regulating neuronal physiology immune cross-talk, its properties adapt to aging. Here, we analyze a research framework where NVU dysfunction, caused by acute insults or disease progression in aging brain, represents converging mechanism underlying late-onset seizures epilepsy neurological neurodegenerative sequelae. Furthermore, seizure activity may accelerate sustaining regional cerebrovascular pathology link comorbidities. Next, focus on diagnostic approaches that could be tailored conditions elderly. We also examine impending disease-modifying strategies based restoration of and, more general, homeostatic control anti- pro-inflammatory players. conclude with an outlook current pre-clinical knowledge gaps clinical challenges pertinent onset population.

Language: Английский

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Astrocyte Involvement in Blood–Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17146 - 17146

Published: Dec. 5, 2023

Neurological disorders have been linked to a defective blood–brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge molecular and signaling mechanisms NVU emergence improved experimental models allow BBB permeability prediction development new brain-targeted therapies. As constituents, astrocytes are most numerous glial cells, characterized heterogeneity that occurs as result developmental context-based gene expression profiles differential non-coding ribonucleic acids (RNAs). Due their dynamic responses different signals, may beneficial or detrimental role BBB’s function, deep effects on pathophysiology (and progression of) central nervous system diseases. The implication astrocytic-derived extracellular vesicles pathological due ability pass BBB, must also be considered. astrocytes’ interaction endothelial cells at level considered promising therapeutic targets neurological conditions. Nevertheless, personalized well-founded approach addressed, temporal spatial reactive astrogliosis states during disease.

Language: Английский

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Endothelial β-Catenin Deficiency Causes Blood-Brain Barrier Breakdown via Enhancing the Paracellular and Transcellular Permeability

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: May 9, 2022

Disruption of the blood-brain barrier (BBB) causes or contributes to neuronal dysfunction and several central nervous system (CNS) disorders. Wnt/β-catenin signaling is essential for maintaining integrity adult BBB in physiological pathological conditions, including stroke. However, how impairment endothelial results breakdown remains unclear. Furthermore, individual contributions different permeability-inducing mechanisms, intercellular junction damage, transcytosis, fenestration, unexplored. Here, we induced β-catenin endothelial-specific conditional knockout (ECKO) mice determined its impact on permeability underlying mechanism. ECKO reduced levels active mRNA Wnt target genes mice, indicating downregulation signaling. displayed severe widespread leakage plasma IgG albumin into cerebral cortex, which was absent wild-type controls. Mechanistically, both paracellular transcellular transport routes were disrupted mice. First, tight protein ultrastructure brain endothelium. Second, substantially increased number vesicles caveolae-mediated transcytosis through downregulating Mfsd2a upregulating caveolin-1 expression. Interestingly, fenestration upregulated expression marker Plvap not observed Overall, our study reveals that maintains

Language: Английский

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The shared role of cholesterol in neuronal and peripheral inflammation

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 249, P. 108486 - 108486

Published: June 29, 2023

Language: Английский

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