amyotrophic lateral sclerosis

Gruppo di ricerca sulla sclerosi laterale amiotrofica

Gruppo di ricerca sulla sclerosi laterale amiotrofica

Il gruppo di ricerca sulla sclerosi laterale amiotrofica si avvale dalla collaborazione decennale tra il centro malattie rare neuromuscolari (Dipartimento di Neuroscienze Umane), il laboratorio di voltage-clamp intracellulare (Dipartimento di Fisiologia e Farmacologia) e l'Unità di Istologia ed Embriologia Medica (Dipartimento di Scienze Anatomiche Istologiche Medico Legali e dell'Apparato Locomotore).

On the relationship between attention processing and P300-based brain computer interface control in amyotrophic lateral sclerosis

Our objective was to investigate the capacity to control a P3-based brain-computer interface (BCI) device for communication and its related (temporal) attention processing in a sample of amyotrophic lateral sclerosis (ALS) patients with respect to healthy subjects. The ultimate goal was to corroborate the role of cognitive mechanisms in event-related potential (ERP)-based BCI control in ALS patients. Furthermore, the possible differences in such attentional mechanisms between the two groups were investigated in order to unveil possible alterations associated with the ALS condition.

Oxidative stress in amyotrophic lateral sclerosis: pathophysiology and opportunities for pharmacological intervention

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2-5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS.

Letter to the editor: autoimmune pathogenic mechanisms in amyotrophic lateral sclerosis

The innate immune system may affect the function and survival of motor neurons in ALS by at least three mechanisms. First, there is evidence to suggest that aggregates of mutant SOD1—which is derived from microglial and astroglial cells—activate neighbouring microglia by binding to TLR2, TLR4, and CD14, and subsequently promote neuronal cell death [9]. Second, the release of pro- inflammatory cytokines may drive motor neuron damage. Third, although poorly understood, a mechanism has been suggested on the basis of the functional analysis of microglial cells that express mutant SOD1 [10].

Metabotropic glutamate receptor involvement in the pathophysiology of amyotrophic lateral sclerosis: new potential drug targets for therapeutic applications

Amyotrophic lateral sclerosis (ALS) is a complex genetic, late age-onset, progressive neurodegenerative disorder leading to the death of upper and lower motor neurons. Life expectancy after diagnosis is short due to the ongoing degeneration and to the lack of effective treatments. Axonal alterations, mitochondrial deficits, RNA changes, protein misfolding and turnover, glial dysfunction and hyperexcitability are key players in molecular mechanisms involved in the degeneration of motor neurons.

Direct conversion of human pluripotent stem cells into cranial motor neurons using a piggyBac vector

Human pluripotent stem cells (PSCs) are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different motor neurons populations show a different susceptibility to degeneration.

Background-deflection Brillouin microscopy reveals altered biomechanics of intracellular stress granules by ALS protein FUS

Altered cellular biomechanics have been implicated as key photogenic triggers in age-related diseases. An aberrant liquid-to-solid phase transition, observed in in vitro reconstituted droplets of FUS protein, has been recently proposed as a possible pathogenic mechanism for amyotrophic lateral sclerosis (ALS). Whether such transition occurs in cell environments is currently unknown as a consequence of the limited measuring capability of the existing techniques, which are invasive or lack of subcellular resolution.

FUS mutant human motoneurons display altered transcriptome and microRNA pathways with implications for ALS pathogenesis

The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analysis of differentially expressed genes identified significant enrichment of pathways previously associated to sporadic ALS and other neurological diseases.

Creatine kinase and progression rate in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no recognized clinical prognostic factor. Creatinine kinase (CK) increase in these patients is already described with conflicting results on prognosis and survival. In 126 ALS patients who were fast or slow disease progressors, CK levels were assayed for 16 months every 4 months in an observational case-control cohort study with prospective data collection conducted in Italy.

Effects of class II-selective histone deacetylase inhibitor on neuromuscular function and disease progression in SOD1-ALS mice

Emerging evidence indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delay ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity toward specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. Here, we tested the effects of the HDAC Class II selective inhibitor MC1568 on disease evolution, motor neuron survival as well as skeletal muscle function in SOD1G93A mice.

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