Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 558 - 558

Published: May 30, 2024

Mood disorders and substance use disorder (SUD) are of immense medical social concern. Although significant progress on neuronal involvement in mood reward circuitries has been achieved, it is only relatively recently that the role glia these attracted attention. Detailed understanding glial functions devastating diseases could offer novel interventions. Here, following a brief review involved regulation perception, specific contributions neurotrophic factors, neuroinflammation, gut microbiota to highlighted. In this context, cells (e.g., microglia, astroglia, oligodendrocytes, synantocytes) phenotypic manifestation or SUD emphasized. addition, knowledge potential development therapeutics touched upon.

Language: Английский

---

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 474 - 474

Published: March 7, 2024

Parkinson’s disease (PD) is a progressive neurodegenerative characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) the primary neurotransmitter involved in this disease, but cholinergic imbalance has been implicated. Current intervention PD focused on replenishing central DA, which provides remarkable temporary symptomatic relief does not address neuronal loss progression of disease. It well established nicotinic receptors (nAChRs) can regulate DA release nicotine itself may have neuroprotective effects. Recent studies identified nAChRs nonneuronal cell types, including glial cells, where they inflammatory responses. Given crucial role neuroinflammation dopaminergic degeneration involvement microglia astrocytes response, provide novel therapeutic target prevention and/or treatment PD. In review, following brief discussion PD, we focus cells and, specifically, their pathology treatment.

Language: Английский

---

Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders

Published: Sept. 13, 2023

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also a seemingly distinct Niemann-Pick type C with primarily juvenile-onset. This strongly argues for an overlap pathogenic mechanisms. The commonly researched include various cell subsets microglia, peripheral macrophages, or regulatory T cells (Tregs), complement system, other soluble factors. In this review, we will compare these from clinical point view out common pathways mechanisms protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We describe approaches treating dysfunctions disorders, moving immunization microbiome regulation stem treatment.

Language: Английский

---

Novel Therapeutic Strategies in Alzheimer’s Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(11), P. 3098 - 3098

Published: May 25, 2024

Alzheimer's disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies for AD, focusing on shortcomings traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades research emphasizing role Aβ accumulation in AD pathogenesis, clinical trials targeting have obtained disappointing results, highlighting complexity pathophysiology need investigating other approaches. In this manuscript, we first discuss challenges associated anti-Aβ therapies, including efficacy potential adverse effects, underscoring necessity alternative mechanisms targets. Thereafter, promising non-Aβ-based strategies, such as tau-targeted neuroinflammation modulation, gene stem cell therapy. These approaches offer new avenues treatment by addressing additional pathological hallmarks downstream effects beyond deposition.

Language: Английский

---

Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1144 - 1144

Published: July 3, 2024

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative characterized by involuntary movements, cognitive decline, executive dysfunction, neuropsychiatric conditions such as anxiety depression. It follows an autosomal dominant inheritance pattern. Thus, child who has parent with the mutated huntingtin (mHTT) gene 50% chance of developing disease. Since HTT protein involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, autophagy, its aberrant aggregates lead to disruption numerous pathways neurodegeneration. Essential heavy metals are vital at low concentrations; however, higher concentrations, they can exacerbate HD disrupting glial–neuronal communication and/or causing dysbiosis (disturbance gut microbiota, GM), both which neuroinflammation further Here, we discuss detail interactions iron, manganese, copper glial–neuron GM indicate how this knowledge may pave way for development new generation disease-modifying therapies HD.

Language: Английский

---

Protein Misfolding and Aggregation as a Mechanistic Link Between Chronic Pain and Neurodegenerative Diseases

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 259 - 259

Published: April 8, 2025

Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) are characterized progressive neuronal loss cognitive or motor decline, often underpinned pathological protein misfolding aggregation. Emerging evidence suggests potential mechanistic link between chronic NDs, with contributing neuroinflammatory states homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis aggregation serve bridge We systematically examine molecular pathways misfolding, proteostasis dysfunction shared neuroimmune mechanisms, highlighting prion-like propagation misfolded proteins, neuroinflammation, oxidative stress common denominators. further discuss from experimental models clinical studies linking accelerated pathology—including tau accumulation, amyloid dysregulation, microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting aggregation, enhancing chaperone function, modulating unfolded response (UPR), attenuating glial activation explored strategies mitigate possibly slow Understanding this intersection not only elucidates pain’s role decline but also interventions addressing inflammation could yield dual benefits management modification.

Language: Английский

---

Intercellular Adhesion Molecule 1 (ICAM-1): An Inflammatory Regulator with Potential Implications in Ferroptosis and Parkinson’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1554 - 1554

Published: Sept. 15, 2024

Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important molecules during leukocyte recruitment. It is encoded by ICAM1 gene and plays central role in inflammation. Its crucial many inflammatory diseases such ulcerative colitis rheumatoid arthritis are well established. Given that neuroinflammation, underscored microglial activation, key element neurodegenerative Parkinson’s disease (PD), we investigated whether ICAM-1 this progressive neurological condition and, if so, to elucidate underpinning mechanisms. Specifically, were interested potential interaction between ICAM-1, glial cells, ferroptosis, an iron-dependent form cell death recently implicated PD. We conclude there exist direct indirect (via cells T cells) influences on ferroptosis further elucidation these interactions can suggest novel intervention for devastating disease.

Language: Английский

---

Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 338 - 338

Published: Feb. 14, 2024

Neurological disorders such as Parkinsonism cause serious socio-economic problems there are, at present, only therapies that treat their symptoms. The well-established hallmark alpha-synuclein (SYN) is enriched in the inclusion bodies characteristic of Parkinsonism. We discovered a prominent partner SYN, termed Tubulin Polymerization Promoting Protein (TPPP), which has important physiological and pathological activities regulation microtubule network promotion SYN aggregation. role TPPP often neglected research, we here attempt to remedy. In normal brain, are expressed endogenously neurons oligodendrocytes, respectively, whilst, an early stage Parkinsonism, soluble hetero-associations these proteins found both cell types. cell-to-cell transmission proteins, central disease progression, provides unique situation for specific drug targeting. Different strategies intervention discovery biomarkers include (i) interface targeting SYN-TPPP hetero-complex; (ii) proteolytic degradation and/or using PROTAC technology; (iii) depletion by miRNA technology. also discuss potential roles phenotype stabilization oligodendrocytes.

Language: Английский

---

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 437 - 437

Published: April 3, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental characterized by severe deficits in social communication and interaction, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life afflicted. Neuronal glial cells have been implicated. It has genetic component but also be triggered environmental factors drugs. For example, prenatal exposure to valproic acid acetaminophen, ingestion propionic acid, increase risk ASD. Recently, epigenetic influences ASD come forefront investigations etiology, prevention, treatment this disorder. Epigenetics refers DNA modifications alter gene expression without making any changes sequence. Although an increasing number pharmaceuticals chemicals are being implicated etiology ASD, here, we specifically focus molecular abovementioned alterations neuronal their potential connection We conclude better understanding these phenomena lead more effective interventions

Language: Английский

---

Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9859 - 9859

Published: Sept. 12, 2024

Histamine (HA), a biogenic monoamine, exerts its pleiotropic effects through four H1R–H4R histamine receptors, which are also expressed in brain tissue. Together with the projections of HA-producing neurons located within tuberomammillary nucleus (TMN), innervate most areas brain, they constitute histaminergic system. Thus, while remaining mediator inflammatory reaction and immune system function, HA acts as neurotransmitter modulator other systems central nervous (CNS). Although detailed causes still not fully understood, neuroinflammation seems to play crucial role etiopathogenesis both neurodevelopmental neurodegenerative (neuropsychiatric) diseases, such autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), Alzheimer’s disease (AD) Parkinson’s (PD). Given increasing prevalence/diagnosis these their socioeconomic impact, need develop effective forms therapy has focused researchers’ attention on brain’s activity related signaling pathways. This review presents current state knowledge concerning involvement CNS development disorders. To this end, roles neurotransmission, neuroinflammation, neurodevelopment discussed.

Language: Английский

---