Molecular Biotechnology, Journal Year: 2022, Volume and Issue: 65(2), P. 252 - 262
Published: May 19, 2022
Language: Английский
Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 211, P. 115522 - 115522
Published: March 28, 2023
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions people worldwide, with both prevalence and incidence increasing age. It characterized by cognitive decline associated, specifically, degeneration cholinergic neurons. The problem this even more fundamental as available therapies remain fairly limited mainly focused on symptoms' relief. Although aetiology remains elusive, two main pathological hallmarks are described: i) presence neurofibrillary tangles formed unfolded protein aggregates (hyperphosphorylated Tau protein) ii) extracellular amyloid-beta peptide. Given complexity surrounding pathogenesis disease, several potential targets have been highlighted interrelated upon its progression, such oxidative stress accumulation metal ions. Thus, advances made development innovative multitarget therapeutical compounds to delay progression restore cell function. This review focuses ongoing research new insights emerging disease-modifying drugs for AD treatment. Furthermore, classical novel biomarkers early diagnosis their role in assisting improvement targeted will also be approached.
Language: Английский
Citations
126
Neurology and Therapy, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 10, 2025
Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, affects millions worldwide, with significant proportion resistant to pharmacological treatments. Surgical interventions have emerged as pivotal in managing drug-resistant epilepsy (DRE), aiming reduce seizure frequency or achieve freedom. Traditional resective surgeries evolved technological advances, enhancing precision and safety. Neurostimulation techniques, such responsive neurostimulation (RNS) deep brain stimulation (DBS), now provide personalized, real-time management, offering alternatives traditional surgery. Minimally invasive ablative methods, laser interstitial thermal therapy (LITT) Magnetic Resonance-guided Focused Ultrasound (MRgFUS), allow for targeted destruction of epileptogenic tissue reduced risks faster recovery times. The use stereo-electroencephalography (SEEG) robotic assistance has further refined surgical precision, outcomes. These advancements mark paradigm shift towards medicine care, promising improved management quality life patients globally. This review outlines the latest innovations surgery, emphasizing their mechanisms clinical implications improve outcomes DRE.
Language: Английский
Citations
2
Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 60(3), P. 1486 - 1498
Published: Dec. 9, 2022
Language: Английский
Citations
45
Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(4), P. e00427 - e00427
Published: July 1, 2024
Language: Английский
Citations
10
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7137 - 7137
Published: April 12, 2023
Alpha-synuclein (α-Syn) is a short presynaptic protein with an active role on synaptic vesicle traffic and the neurotransmitter release reuptake cycle. The α-Syn pathology intertwines formation of Lewy Bodies (multiprotein intraneuronal aggregations), which, combined inflammatory events, define various α-synucleinopathies, such as Parkinson’s Disease (PD). In this review, we summarize current knowledge mechanistic pathways to inflammation, well eventual microbial dysbiosis α-Syn. Furthermore, explore possible influence mitigation conclusion, given rising burden neurodegenerative disorders, it pressing clarify pathophysiological processes underlying in order consider existing low-grade chronic states potential pathway toward management prevention conditions, aim starting search for concrete clinical recommendations particular population.
Language: Английский
Citations
16
Brain Research Bulletin, Journal Year: 2023, Volume and Issue: 199, P. 110673 - 110673
Published: May 29, 2023
Huntington's disease (HD) is a neurodegenerative disorder caused by an autosomal dominant mutation leading to abnormal CAG repeat expansion. The result the synthesis of toxic misfolded protein, called mutant huntingtin protein (mHTT). Most current treatments are palliative, but latest research has expanded into multiple modalities, including stem cells, gene therapy, and even use 3D cell structures, organoids. Stem as treatment for HD included various types such mesenchymal neural embryonic reprogrammed cells induced pluripotent cells. goal been develop transplant grafts that will replace existing mutated neurons, well release trophic factors neuronal support. Additionally, in modification using CRISPR-Cas9, PRIME editing, other forms genetic modifications continuing evolve. recently, advancements modeling have yielded tissue models, These organoids offer unique opportunity structured graft which, ideally, models normal human brain more accurately. This manuscript summarizes recent modifications, potential HD.
Language: Английский
Citations
12
International Journal of Current Pharmaceutical Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10
Published: Jan. 15, 2025
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder primarily affecting individuals over 60. It multifactorial driven by both modifiable factors, such as lifestyle, diet, and prior health conditions, well non-modifiable like age, genetics, family history. The key pathological features of AD include the buildup amyloid β plaques neurofibrillary tangles resulting from hyperphosphorylated tau proteins in brain. Biomarkers protein levels cerebrospinal fluid (CSF) blood are essential for diagnosing tracking progression. Current research focuses on developing drugs targeting multiple aspects pathology, including inflammation, oxidative stress, synaptic dysfunction, accumulation. These treatments aim to slow cognitive decline neuronal damage. Given complexity AD, multi-targeted therapeutic approaches being explored enhance treatment efficacy. This review provides an overview risk biomarkers used diagnosis, latest advances clinical drug development.
Language: Английский
Citations
0
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: Jan. 31, 2025
Seizures is a prevalent neurological disorder with largely elusive pathogenesis. In this study, we identified the key gene RACK1 and its novel mutation RACK1-p.L206P as being associated seizures through single-cell transcriptome sequencing (scRNA-seq) whole exome (WES) techniques. Our findings reveal that significantly enhances proliferation, migration, phagocytic ability, inflammatory activation in human microglia, which turn affects neuronal excitability synaptic function, culminating typical seizure symptoms seizures. These effects were further validated mouse model using CRISPR/Cas9 editing technology. Mutant microglia exhibited increased induced apoptosis hippocampal neurons, leading to higher action potential frequency excitatory marker expression. vivo experiments demonstrated mutant mice displayed classic symptoms, tendency for bursts during initial depolarization, along more frequent spike discharges. Additionally, synapse density size CA1 region of elevated, accompanied by expression VGLUT1 PSD95 within microglia. This study offers insights into molecular mechanisms underlying presents valuable clues development future therapeutic strategies.
Language: Английский
Citations
0
Science Bulletin, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
0
Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13
Published: March 21, 2025
Introduction: Leukocyte adhesion deficiency type 1 (LAD1) is a severe inborn error of immunity caused by mutations in the ITGB2 gene, which encodes beta-2 integrin subunit (CD18). These lead to absence or CD18/CD11a, b, and c heterodimers, crucial for leukocyte immune function. CRISPR-Cas9 Gene editing technology represents promising approach correcting these genomic defects restore stable expression CD18 reverse disease. Methods: We developed CRISPR-Cas9-based gene correction strategy using Jurkat cells patient-derived lymphoblastoid cell lines as surrogates hematopoietic progenitor cells. Three candidate gRNAs were first predicted silico CRISPOR experimentally tested wild-type ITGB2-expressing identify gRNA with highest DNA cleavage efficiency. The most efficient was then paired espCas9 used alongside five homology-directed repair templates (HDRs) (single-stranded donor oligonucleotides, ssODNs) lines. levels edited quantified via flow cytometry, whole-genome sequencing (WGS) conducted assess off-target effects insertion accuracy. Results: Among three gRNAs, 2-rev exhibited rate Using this HDR-2, we achieved 23% restoration LAD1 cells, level sufficient change disease course from moderate. Whole-genome confirmed undesired insertions, demonstrating high specificity precision correction. Discussion: This method provides precise effective patients. high-fidelity process, validated through WGS, supports its potential future applications CD34+ stem therapies. can be further optimized clinical translation, offering path toward long-term cure LAD1.
Language: Английский
Citations
0