Dendrimers in Neurodegenerative Diseases

Processes, Год журнала: 2023, Номер 11(2), С. 319 - 319

Опубликована: Янв. 18, 2023

Neurodegenerative diseases (NDs), such as Parkinson’s Disease (PD), Alzheimer’s (AD), Multiple Sclerosis (MS) and amyotrophic lateral sclerosis (ALS), are characterized by progressive loss of structure or function neurons. Current therapies for NDs only symptomatic long-term ineffective. This challenge has promoted the development new against relevant targets in these pathologies. In this review, we will focus on most promising therapeutic approaches based dendrimers (DDs) specially designed treatment diagnosis NDs. DDs well-defined polymeric structures that provide a multifunctional platform developing different nanosystems myriad applications. have been proposed interesting drug delivery systems with ability to cross blood–brain barrier (BBB) increase bioavailability classical drugs brain, well genetic material, reducing synthesis specific targets, β-amyloid peptide. Moreover, shown be anti-amyloidogenic amyloid-β peptide (Aβ) Tau aggregation, powerful agents blocking α-synuclein (α-syn) fibrillation, exhibit anti-inflammatory properties, promote cellular uptake certain cell types, potential tools ND diagnosis. summary, emerged alternatives current since they may limit extent damage neuroprotection affected tissues.

Язык: Английский

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Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(1), С. 823 - 823

Опубликована: Янв. 3, 2023

Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease development to break. Protein misfolding considered the most important pathogenetic factor diseases. Physiological mechanisms related function chaperones, which contribute restoration native conformation functionally proteins, evolved evolutionarily. These can be promising for pharmacological regulation. Therefore, aim this review was analyze endoplasmic reticulum stress (ER stress) unfolded protein response (UPR) in pathogenesis Data on BiP Sigma1R chaperones clinical experimental studies Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, Huntington's are presented. The possibility neuroprotective effect dependent ligand activation these also demonstrated. interaction between BiP-associated signaling neuroprotection discussed. performed analysis suggests feasibility regulation chaperone function, order achieve a effect, need further conjugation cellular controlled by chaperones.

Язык: Английский

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Aquaporin-4 and Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1672 - 1672

Опубликована: Янв. 30, 2024

The water-selective channel aquaporin-4 (AQP4) is implicated in water homeostasis and the functioning of glymphatic system, which eliminates various metabolites from brain tissue, including amyloidogenic proteins. Misfolding α-synuclein protein its post-translational modifications play a crucial role development Parkinson’s disease (PD) other synucleopathies, leading to formation cytotoxic oligomers aggregates that cause neurodegeneration. Human animal studies have shown an interconnection between AQP4 dysfunction accumulation; however, specific these mechanisms remains unclear. This review summarizes current knowledge on progression pathology, considering possible effects dysregulation molecular can impact modification, accumulation aggregation. It also highlights future directions help study protective during PD neurodegenerative diseases.

Язык: Английский

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Upregulated ECM genes and increased synaptic activity in Parkinson’s human DA neurons with PINK1/ PRKN mutations

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Май 18, 2024

Abstract Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. Primary symptoms of PD arise with loss dopaminergic (DA) neurons in Substantia Nigra Pars Compacta, but also affects hippocampus and cortex, usually its later stage. Approximately 15% cases are familial a genetic mutation. Two associated genes autosomal recessive (AR) early-onset PINK1 PRKN . In vitro studies these mutations needed to understand neurophysiological changes patients’ that may contribute neurodegeneration. this work, we generated differentiated DA hippocampal from human induced pluripotent stem cells (hiPSCs) derived two patients double mutation their (one homozygous one heterozygous) assessed neurophysiology compared healthy controls. We showed synaptic activity impaired neurons. Mutant had enhanced excitatory post-synaptic activity. addition, exhibited more pronounced electrophysiological differences control Signaling network analysis RNA sequencing results revealed Focal adhesion ECM receptor pathway were top upregulated pathways mutant Our findings reveal phenotypes linked differ those other mutations, suggesting unique interplay between drives different mechanisms.

Язык: Английский

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Application of Nanobiosensor Engineering in the Diagnosis of Neurodegenerative Disorders

Results in Engineering, Год журнала: 2024, Номер 24, С. 102790 - 102790

Опубликована: Сен. 5, 2024

Язык: Английский

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