Neuropathology of incidental Lewy body & prodromal Parkinson’s disease

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: May 12, 2023

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with loss of dopaminergic (DA) neurons. Despite symptomatic therapies, there currently no disease-modifying treatment to halt neuronal in PD. A major hurdle for developing and testing such curative therapies results from the fact that most DA neurons are already lost at time clinical diagnosis, rendering them inaccessible therapy. Understanding early pathological changes precede Lewy body pathology (LBP) cell PD will likely support identification novel diagnostic therapeutic strategies help differentiate LBP-dependent -independent alterations. Several previous studies identified specific molecular cellular occur prior appearance bodies (LBs) neurons, but concise map events missing. Methods Here, we conducted literature review identify discuss investigated cases incidental (iLBD), presumed precursor Results Collectively, our demonstrates numerous neuropathological occurring LBs Conclusions Our provides reader summary may targets aid development

Language: Английский

---

The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson’s Disease Pathogenesis

Nutrients, Journal Year: 2023, Volume and Issue: 15(16), P. 3585 - 3585

Published: Aug. 15, 2023

Parkinson’s disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, no cure available. Recently, it has been proposed that insulin resistance (IR) could be central factor in development. IR associated with neuropathological features like α-synuclein aggregation, loss, neuroinflammation, mitochondrial dysfunction, autophagy. These related impaired metabolism, death, aggravation Moreover, pharmacological options involve signaling improvement non-dopaminergic strategies have under drugs prevent metabolic pathways involved damage. All these approaches improve outcomes. Also, new biomarker identification may allow for an earlier diagnosis high-risk individuals. review describes main implicated development involving IR. presents several therapeutic directed at used treatment. The understanding molecular mechanisms neurodegenerative enhance diagnosis.

Language: Английский

---

An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12464 - 12464

Published: Aug. 5, 2023

While a certain level of inflammation is critical for humans to survive infection and injury, prolonged inflammatory response can have fatal consequences. Pattern recognition Toll-like receptors (TLRs) are key players in the initiation an process. TLR2 one most studied pattern (PRRs) known form heterodimers with either TLR1, TLR4, TLR6, TLR10, allowing it recognize wide range pathogens. Although large number studies been conducted over past decades, there still many unanswered questions regarding mechanisms health disease. In this review, we provide up-to-date overview TLR2, including its homo- heterodimers. Furthermore, will discuss pro- anti-inflammatory properties recent findings prominent TLR2-associated infectious neurodegenerative diseases.

Language: Английский

---

Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286

Published: Feb. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Language: Английский

---

Immunosenescence and Inflammaging: Mechanisms and Role in Diseases

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102540 - 102540

Published: Oct. 10, 2024

Language: Английский

---

Modulating α-synuclein propagation and decomposition: Implications in Parkinson's disease therapy

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102319 - 102319

Published: May 6, 2024

Language: Английский

---

Brain MRI Detection of an Abnormal Peak Width of Skeletonized Mean Diffusivity in REM Sleep Behavior Disorder

Journal of Neuroimaging, Journal Year: 2025, Volume and Issue: 35(1)

Published: Jan. 1, 2025

ABSTRACT Background and Purpose Peak width of skeletonized mean diffusivity (PSMD) is a novel marker white matter damage, which may be related to small vessel disease. This study aimed investigate the presence damage in patients with isolated rapid eye movement sleep behavior disorder (RBD) using PSMD. Methods We enrolled newly diagnosed RBD confirmed by polysomnography age‐ sex‐matched healthy controls. Diffusion tensor imaging (DTI) was conducted 3‐Tesla MRI scanner. measured PSMD based on DTI several steps, including preprocessing, skeletonization, application custom mask, histogram analysis, Functional Magnetic Resonance Imaging Brain Software Library program. compared incidence between controls performed correlation analysis clinical factors RBD. Results Thirty 41 were enrolled. The significantly higher than that (3.078 vs. 2.746 × 10 −4 mm 2 /s, p = 0.001). In addition, positively correlated age ( r 0.477, 0.007). However, not associated other or polysomnographic factors. Conclusion Patients had controls, indicating evidence finding highlights potential as for detecting diseases, disorders.

Language: Английский

---

Flavonoids in the regulation of microglial-mediated neuroinflammation; focus on fisetin, rutin, and quercetin

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114537 - 114537

Published: March 1, 2025

Language: Английский

---

Recombinant Antibody Fragments for Immunotherapy of Parkinson’s Disease

BioDrugs, Journal Year: 2024, Volume and Issue: 38(2), P. 249 - 257

Published: Jan. 27, 2024

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Multiple genetic and environmental factors leading to progressive loss of dopaminergic neurons in substantia nigra pars compacta (SN) consequent depletion dopamine were described. Current clinical approaches, such as replacement or deep brain stimulation using surgically implanted probes, provide symptomatic relief but cannot modify progression. Therefore, disease-modifying therapeutic tools are urgently needed. Immunotherapy including passive transfer protective antibodies their fragments, have shown efficacy several animal models diseases, PD. Recombinant antibody fragments promising alternatives conventional full-length antibodies. Modern computational approaches molecular biology tools, directed evolution methodology, design tissue-penetrating fusion peptides allowed for development recombinant with superior specificity affinity, reduced immunogenicity, capacity target hidden epitopes cross blood-brain barrier (BBB), higher solubility stability, ability refold after heat denaturation, inexpensive large-scale production. In addition, do not induce microglia Fcγ receptor (FcγR)-mediated proinflammatory response tissue damage central nervous system (CNS), because they lack Fc portion immunoglobulin molecule. present review, we summarized data on evaluated immunotherapeutics preclinical PD discussed potential developing preventive protocols patients

Language: Английский

---

Optimization Of The Search For Neuroprotectors Among Bioflavonoids

Published: June 11, 2024

For the first time to optimize creation of new neuroprotective agents based on bioflavonoids, we applied information technologies - docking analysis calculate binding candidate molecules pharmacological target protein transthyretin, as well program virtual screening NO scavengers. As a result this approach, substance catechin was isolated from quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, B2, B3, Catechin-3-gallate according analysis. screening, identified potential scavenger (55.15% prediction). The results prediction were confirmed by in vitro experiments. Course administration animals with experimental multiple sclerosis (MS) against background methylprednisolone completely eliminated lethal cases, reduced number diseased 20%, prevented development severe neurological symptoms 20% (compared group) and 60% compared control group. leads decrease neurodegradation markers cytosol rats EAE: NSE 37%, S-100 54.8%. combined significantly exceeds combination reference drug mexidol degree reduction. obtained indicate significant effect ocular combinations catechin. above-mentioned confirms correctness bioflavonoid selection help program.

Language: Английский

---