Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3866 - 3866

Published: Feb. 15, 2023

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral (ALS), are characterized by acute or chronic progressive loss of one several neuronal subtypes. However, despite their increasing prevalence, little progress has been made in successfully treating these diseases. Research recently focused on neurotrophic factors (NTFs) as potential regenerative therapy for neurodegenerative Here, we discuss the current state knowledge, challenges, future perspectives NTFs with a direct effect inflammatory degenerative disorders. Various systems delivery NTFs, such stem immune cells, viral vectors, biomaterials, have applied to deliver exogenous central nervous system, promising results. The challenges that currently need be overcome include amount delivered, invasiveness route, blood-brain barrier permeability, occurrence side effects. Nevertheless, it is important continue research develop standards clinical applications. In addition use single complexity diseases may require combination therapies targeting pathways other possibilities using smaller molecules, NTF mimetics, effective treatment.

Language: Английский

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Neuroprotective Effects of Lactoferrin in Alzheimer’s and Parkinson’s Diseases: A Narrative Review

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: March 30, 2023

Recent advancements in lactoferrin research have uncovered that does function not only as an antimicrobial protein but also immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how interacts the brain, specifically its effects mechanisms against Alzheimer's Parkinson's diseases (AD PD), two most common neurodegenerative diseases. The pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) receptor (LfR)), signaling (extracellular regulated kinase-cAMP response element-binding (ERK-CREB) phosphoinositide 3-kinase/Akt (PI3K/Akt)), effector proteins (A disintegrin metalloprotease10 (ADAM10) hypoxia-inducible factor 1α (HIF-1α)) cortical/hippocampal dopaminergic neurons are described. These cellular of likely responsible for attenuating cognitive motor deficits, amyloid-β α-synuclein accumulation, neurodegeneration animal models AD PD. This discusses inconsistent findings related to AD. Overall, contributes existing by clarifying potential context PD neuropathology.

Language: Английский

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Oral administration of silybin protects against MPTP-induced neurotoxicity by reducing pro-inflammatory cytokines and preserving BDNF levels in mice

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 14, 2023

Abstract Parkinson’s disease (PD) is the second most frequent neurodegenerative associated with motor dysfunction secondary to loss of dopaminergic neurons in nigrostriatal axis. Actual therapy consists mainly levodopa; however, its long-term use promotes effects. Consequently, finding new therapeutic alternatives, such as neuroprotective molecules, necessary. Among these alternatives silybin (Sb), major bioactive flavonolignan silymarin. Both exert effects, preserving dopamine levels and when administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model, being probably Sb potential molecule behind this effect. To elucidate role we determined dose-dependent conservation striatal content following oral administration. Then, evaluated deficit tests using best conservative dose a cytokine-dependent inflammatory profile status, malondialdehyde an oxidative stress product, neurotrophic factors MPTP-induced model. Our results show that at 100 mg/kg conserved about 60% levels. Also, improved deficits, preserved mitochondrial function, reduced lipid peroxidation, diminished proinflammatory cytokines basal levels, enhanced fractalkine production striatum substantia nigra, increased IL-10 IL-4 nigra MPTP mice. Thus, may be pharmacological treatment alternative.

Language: Английский

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The role of platelets in the blood-brain barrier during brain pathology

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 8, 2024

Platelets play critical roles in maintaining hemostasis. The blood brain barrier (BBB), a significant physical and metabolic barrier, helps maintain physiological stability by limiting transportations between the neural tissues. When undergoes inflammation, tumor, trauma, or bleeding, platelet responses to help with BBB homeostasis. In traditional point of view, activated platelets aggregate form thrombi which cover gaps vessels protect BBB. However, increasing evidences indicate that may harm enhancing vascular permeability. Hereby, we reviewed recently published articles special focus on platelet-mediated damage Factors released can induce permeability, involve platelet-activating factors (PAF), P-selectin, ADP, platelet-derived growth (PDGF) superfamily proteins, especially PDGF-AA PDGF-CC, etc. also secrete Amyloid-β (Aβ), triggers neuroinflammation downregulates expression tight junction molecules such as claudin-5 Additionally, aggregates neutrophils release reactive oxygen species (ROS), destroy DNA, lipids endothelial cells (ECs). Moreover, participate affect Conversely, some PDGF-BB, protects summary, dual integrity related mechanisms are reviewed.

Language: Английский

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Some Novel Therapies in Parkinson’s Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 549 - 549

Published: Feb. 29, 2024

In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need development novel to alleviate symptoms PD retardation or halt progression itself. This systematic review aims critically update some most promising treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations future directions in research. Gene therapy encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, neuronal circuits animal clinical trials. A approach delivery involves use nanotechnology create vehicles that can traverse blood-brain barrier deliver medications specifically regions brain affected by PD. Neuroprotective agents are compounds have ability protect neurons from degeneration death, they hold great promise evolution disease-modifying Magnetic field a non-invasive method promotes neural plasticity The establishment standardized protocols human studies, safety, ethical considerations, cost-effectiveness major challenges research therapies. represents path toward effective personalized

Language: Английский

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From lab bench to hope: a review of gene therapies in clinical trials for Parkinson’s disease and challenges

Neurological Sciences, Journal Year: 2024, Volume and Issue: 45(10), P. 4699 - 4710

Published: May 25, 2024

Language: Английский

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Superparamagnetic iron oxide-enclosed hollow gold nanostructure with tunable surface plasmon resonances to promote near-infrared photothermal conversion

Advanced Composites and Hybrid Materials, Journal Year: 2022, Volume and Issue: 5(3), P. 2387 - 2398

Published: March 15, 2022

Language: Английский

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PPARs and Their Neuroprotective Effects in Parkinson’s Disease: A Novel Therapeutic Approach in α-Synucleinopathy?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3264 - 3264

Published: Feb. 7, 2023

Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD misfolding and propagation α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, synaptic leading to neurodegeneration. To this date, there are no disease-modifying drugs generate neuroprotection against these neuropathological events especially α-synucleinopathy. Growing evidence suggests peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects PD, however, whether they also an anti-α-synucleinopathy effect unknown. Here we analyze reported therapeutic PPARs, specifically gamma isoform (PPARγ), preclinical animal models clinical trials for suggest possible mechanisms acting downstream from receptors. Elucidating PPARs through mimic as closely will facilitate execution better PD.

Language: Английский

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The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107101 - 107101

Published: Feb. 7, 2024

The vascular endothelial growth factors (VEGFs) and their cognate receptors (VEGFRs), besides well-known involvement in physiological angiogenesis/lymphangiogenesis diseases associated to pathological vessel formation, play multifaceted functions the central nervous system (CNS). In addition shaping brain development, by controlling cerebral vasculogenesis regulating neurogenesis as well astrocyte differentiation, VEGFs/VEGFRs axis exerts essential adult both contexts. this article, after describing CNS, we focus on neurodegenerative reviewing current literature rather complex contribution pathogenic mechanisms of Alzheimer's (AD) Parkinson's (PD) diseases. Thereafter, based outcome targeting animal models AD PD, discuss factual relevance pharmacological modulation a novel potential disease-modifying approach for these pathologies. Specific VEGFRs targeting, aimed at selective VEGFR-1 inhibition, while preserving VEGFR-2 signal transduction, appears promising strategy hit molecular underlying pathology. Moreover, therapeutic VEGFs-based approaches can be proposed PD treatment, with aim fine-tuning levels amplify neurotrophic/neuroprotective effects limiting an excessive impact permeability.

Language: Английский

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Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

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