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Therapeutic advances in neural regeneration for Huntington’s disease

Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito annamaria cimini Michele d’Angelo Department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, num

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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The emerging role of probiotics in neurodegenerative diseases:new hope for Parkinson’s disease?

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Neural Regeneration Research 2021年第4期16卷 628-634页

作者： Vanessa Castelli Michele d’Angelo Massimiliano Quintiliani Elisabetta Benedetti Maria Grazia Cifone annamaria cimini Department of Life Health and Environmental SciencesUniversity of L’AquilaItaly SIRE Srl NaplesItaly Sbarro Institute for Cancer Research and Molecular Medicine Department of BiologyTemple UniversityPhiladelphiaPAUSA

Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.

关键词： age-related diseases brain dysbiosis gut-brain axis microbiota neurodegeneration nutraceuticals Parkinson’s disease probiotics SLAB51

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