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Special Issue “Neurogenetics in Neurology”
No full textWith the rapid developments in molecular genetics and genomics, this Special Issue collates works outlining ultra-modern scientific research [...
Hereditary spastic paraplegia: Genetic heterogeneity and common pathways
No full textHereditary Spastic Paraplegias (HSPs) are a heterogeneous group of disease, mainly characterized by progressive spasticity and weakness of the lower limbs resulting from distal degeneration of corticospinal tract axons. Although HSPs represent rare or ultra-rare conditions, with reported cases of mutated genes found in single families, overall, with 87 forms described, they are an important health and economic problem for society and patients. In fact, they are chronic and life-hindering conditions, still lacking a specific therapy. Notwithstanding the number of forms described, and 73 causative genes identified, overall, the molecular diagnostic rate varies among 29% to 61.8%, based on recent published analysis, suggesting that more genes are involved in HSP and/or that different molecular diagnostic approaches are necessary. The accumulating data in this field highlight several peculiar features of HSPs, such as genetic heterogeneity, the discovery that different mutations in a single gene can be transmitted in dominant and recessive trait in families and allelic heterogeneity, resulting in the involvement of HSP-genes in other conditions. Based on the observation of protein functions, the activity of many different proteins encoded by HSP-related genes converges into some distinct pathophysiological mechanisms. This suggests that common pathways could be a potential target for a therapy, possibly addressing several forms at once. Furthermore, the overlap of HSP genes with other neurological conditions can further expand this concept
Elevated beta-N-acetylhexosaminidase activity in focal dystonia fibroblasts
No full textSpecific activities of beta-D-hexosaminidase, alpha-D-mannosidase, beta-D-galactosidase and beta-D-glucuronidase were determined in fibroblasts of patients with writer's cramp and torticollis. These diseases show degenerative neurological disorders similar to those observed in lysosomal diseases. Hexosaminidase specific activities, determined using 4-methylumbelliferyl-beta-N-acetylglucopyranoside and 4-methylumbelliferyl-beta-N-acetylglucopyranoside-6-sulphate as substrates, were significantly higher in the fibroblasts of patients than in controls. No significant differences were observed in the specific activities of the other lysosomal enzymes. The increased hexosaminidase specific activities in torticollis and writer's cramp may be additional markers for these diseases
RNA interference as a tool for Alzheimer's disease therapy
No full textRNA interference is a biological process that controls gene silencing in all living cells. Targeting the RNA interference system represents a novel therapeutic strategy able to intercede with multiple disease-related genes and to target many neurodegenerative diseases. Recently, the design of small interfering RNA-selective compounds has become more straightforward because of the significant progress made in predictive modeling for new therapeutic approaches. Although in vivo delivery of RNA interference remains a significant obstacle, new data show that RNAi blocks gene function in vivo, suggesting a potential therapeutic approach for humans. Some groups have demonstrated the efficacy of RNAi therapy in Alzheimer's disease. Results, based on animal models, show a down-regulation of the amyloid precursor protein and a consequent reduction of the amyloid-beta peptide accumulation in the brain or the inactivation of beta-secretase (BACE1). Indeed, lentiviral vectors expressing siRNAs targeting BACE1 reduce amyloid production and the neurodegenerative and behavioural deficit in APP transgenic mice. This review highlights recent advances in RNA research and focuses on strengths and weaknesses of RNAi compounds in Alzheimer's disease
β-N-Acetylhexosaminidase in Peripheral Blood Lymphocytes and Monocytes in the Different Forms and Stages of Multiple Sclerosis
No full textExperimental Cell Models for Investigating Neurodegenerative Diseases
No full textExperimental models play a pivotal role in biomedical research, facilitating the understanding of disease mechanisms and the development of novel therapeutics. This is particularly true for neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and motor neuron disease, which present complex challenges for research and therapy development. In this work, we review the recent literature about experimental models and motor neuron disease. We identified three main categories of models that are highly studied by scientists. In fact, experimental models for investigating these diseases encompass a variety of approaches, including modeling the patient’s cell culture, patient-derived induced pluripotent stem cells, and organoids. Each model offers unique advantages and limitations, providing researchers with a range of tools to address complex biological questions. Here, we discuss the characteristics, applications, and recent advancements in terms of each model system, highlighting their contributions to advancing biomedical knowledge and translational research
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