The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: April 12, 2024

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) certain stimuli such as trauma, infection, and neurodegenerative diseases. This is cellular immune response whereby glial cells are activated, inflammatory mediators liberated reactive oxygen nitrogen species synthesized. key process that helps protect brain from pathogens, but inappropriate, or protracted inflammation yields pathological states Parkinson’s disease, Alzheimer’s, Multiple Sclerosis, other disorders showcase various pathways neurodegeneration distributed in parts CNS. review reveals major neuroinflammatory signaling associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, stem cell therapy, genetic intervention, nanoparticles, aiming regulate neuroinflammation potentially impede decelerate advancement these conditions. A comprehensive understanding intricate connection between diseases pivotal for development future treatment strategies can alleviate burden imposed by devastating disorders.

Language: Английский

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Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 160, P. 114378 - 114378

Published: Feb. 10, 2023

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology ALS still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, neuroinflammation may be involved in pathogenesis From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) Quinidine sulfate (Q), Edaravone, Sodium phenylbutyrate Taurursodiol (PB/TUDCO) achieved FDA approval for treatment. Despite use these four approved agents, survival quality life patients low. Thus, finding novel treatments an urgent requirement. Masitinib, tyrosine kinase inhibitor, emphasizes neuro-inflammatory activity by targeting macrophages, mast cells, microglia cells. Masitinib downregulates proinflammatory cytokines, indirectly reduces inflammation, induces neuroprotection. Also, it was effective phase 2/3 3 trials (CTs) increasing overall delaying motor, bulbar, respiratory function deterioration. This review describes pathophysiology ALS, focusing on Masitinib's mechanism action explaining why could promising actor treatment patients. In addition, CTs other competitor drugs been discussed.

Language: Английский

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Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(4), P. 3315 - 3332

Published: April 7, 2023

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, fasciculations—and survival 3 to 5 years following diagnosis. In review, we performed literature search provide an update on etiology pathophysiological mechanisms involved ALS. There are two types ALS: familial form with genetic involvement, sporadic multifactorial origin. ALS pathophysiology characterized by involvement multiple processes, including oxidative stress, glutamate excitotoxicity, neuroinflammation. Moreover, it proposed that conditioning risk factors affect development, such as susceptibility neurodegeneration neurons, intensity physical activity, intestinal dysbiosis enteric nervous system, which supports existing theories generation. To improve patients’ prognosis survival, necessary further deepen our understanding etiopathogenesis

Language: Английский

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The role of glycogen synthase kinase 3 beta in neurodegenerative diseases

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Sept. 15, 2023

Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), so on. They are characterized by progressive loss or dysfunction neurons in central peripheral nervous system share several cellular molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase that believed play pivotal role pathogenesis NDDs. Here we summarize structure physiological functions GSK3β explore its involvement We also discussed potential as therapeutic target.

Language: Английский

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Distribution of Iron, Copper, Zinc and Cadmium in Glia, Their Influence on Glial Cells and Relationship with Neurodegenerative Diseases

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(6), P. 911 - 911

Published: June 5, 2023

Recent data on the distribution and influence of copper, zinc cadmium in glial cells are summarized. This review also examines relationship between those metals their role neurodegenerative diseases like Alzheimer disease, multiple sclerosis, Parkinson disease Amyotrophic lateral which have become a great challenge for today’s physicians. The studies suggest that among cells, iron has highest concentration oligodendrocytes, copper astrocytes glia hippocampus cortex. Previous shown neurotoxic effects manganese, while can bidirectional effect, i.e., but neuroprotective depending dose state. point to association with neurodegeneration through modulation protein aggregation. Metals accumulate brain aging may be associated age-related diseases.

Language: Английский

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Investigating Edaravone Use for Management of Amyotrophic Lateral Sclerosis (ALS): A Narrative Review

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 13, 2023

The use of Edaravone, given orally, for the treatment amyotrophic lateral sclerosis (ALS) was officially approved by Federal Drug Association (FDA) in 2017. ALS is a rare and progressive degenerative disease that worsens over time. It attacks destroys nerve cells control voluntary muscles, thus leading to weakness, eventual paralysis, and, ultimately death. Edaravone initially intravenously, but recent evidence shows better results with oral suspension. This narrative review aimed investigate benefit management ALS, compare it Riluzole, discuss its mechanism action, route use, side effects, future implications this pharmacotherapy.

Language: Английский

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Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 957 - 957

Published: March 21, 2023

Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors commonly suffer from cerebrovascular disease, with evidence pathological alterations in their small cerebral blood vessels. Impaired brain has detrimental effects on motor neurons: endothelial growth factor levels are lowered ALS, which can compromise cell formation integrity blood–brain barrier. Increased turnover neurovascular unit cells precedes senescence, which, together pericyte alterations, further fosters failure toxic metabolite removal. We here provide a comprehensive overview pathogenesis impaired how novel magnetic resonance imaging techniques aid detection. In particular, we discuss patterns supply cortex number branches anterior middle arteries acting as marker resistance resilience against downstream events ALS. outline certain interventions adapted patient needs capabilities have potential mechanistically target microvasculature towards favorable patterns. Through this strategy, aim guide approaches management better understanding pathophysiology.

Language: Английский

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Multipharmacophore strategy in medicinal chemistry for the design of drugs for the treatment of Alzheimer’s and some other neurodegenerative diseases

Russian Chemical Bulletin, Journal Year: 2023, Volume and Issue: 72(1), P. 130 - 147

Published: Jan. 1, 2023

Language: Английский

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Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics

Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1582 - 1582

Published: Oct. 26, 2023

Amyotrophic lateral sclerosis (ALS) is a fatal condition characterized by the selective loss of motor neurons in cortex, brainstem, and spinal cord. Muscle involvement, muscle atrophy, subsequent paralysis are among main features this disease, which defined as neuromuscular disorder. ALS persistently progressive continue to degenerate, individuals with experience gradual decline their ability perform daily activities. Ultimately, function may result paralysis, presenting significant challenges mobility, communication, self-care. While majority research has traditionally focused on pathogenic pathways central nervous system, there been great interest research. These studies were carried out patients animal models order better understand molecular mechanisms involved develop therapies aimed at improving function. This review summarizes discusses role muscle, well examines recent development treatments.

Language: Английский

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Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies

Cells, Journal Year: 2024, Volume and Issue: 13(7), P. 606 - 606

Published: March 30, 2024

In vitro and preclinical in vivo research the last 35 years has clearly highlighted crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes satellite cells/Schwann cells central peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders painful conditions have therefore been successfully identified, including receptors enzymes, mediators neuroinflammation. However, translation these promising data a clinical setting is often hampered by both technical biological difficulties, making it necessary perform experiments on human models diseases. this review we will, therefore, summarize most relevant contribution pathologies their modulation based obtained post-mortem tissues iPSC-derived brain organoids. The possibility an visualization glia reaction neuroinflammation patients will be also discussed.

Language: Английский

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