Neurological disorders are still one of the major causes of death,and the vast need to find efficacious therapy is nowadays an essential goal of the scientific community.For Parkinson's disease(PD),amyotrophic lat...Neurological disorders are still one of the major causes of death,and the vast need to find efficacious therapy is nowadays an essential goal of the scientific community.For Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),spinal cord injury,and intracerebral hemorrhage.展开更多
Amyotrophic lateral sclerosis(ALS)is a highly aggressive adult-onset neurodegenerative disease caused by the progressive loss of upper and lower motor neurons.Clinically,it causes irreversible muscle atrophy and spast...Amyotrophic lateral sclerosis(ALS)is a highly aggressive adult-onset neurodegenerative disease caused by the progressive loss of upper and lower motor neurons.Clinically,it causes irreversible muscle atrophy and spasticity,leading to death due to respiratory failure,usually within 2–5 years after the first symptom onset.Approximately 85%of ALS cases are classified as sporadic,while the remaining 15%are of familial origin,but the overall clinical and molecular features of the disease are almost undistinguishable in the two forms.The majority of familial ALS cases are caused by pathogenic variants of C9orf72,SOD1,TARDBP,FUS,ANG and OPTN genes that are inherited by a Mendelian pattern and display high penetrance(Kiernan et al.,2020).展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease typically leading to death within 5 years from symptom onset. ALS familial forms are associated with mutations in several genes, including Superoxide...Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease typically leading to death within 5 years from symptom onset. ALS familial forms are associated with mutations in several genes, including Superoxide Dismutase 1 (SOD1) and Fused in Sarcoma (FUS). Although genes linked to ALS participate in disparate biological processes, ALS genetic variants largely trigger shared pathogenic events such as oxidative stress, protein aggregation and defects in RNA processing. Moreover, ALS patients show systemic hypermetabolism that leads to increased energy expenditure at rest and thus weight loss during the disease course.1 ALS hypermetabolic phenotype and weight loss have been extensively characterized in mice bearing the G93A substitution in SOD1 protein (SOD1-G93A), which exhibit skeletal-muscle metabolic reprogramming before disease onset.展开更多
基金“Re Nic ALS” grant from Ari SLA–Fondazione Italiana di ricerca per la SLA to SA。
文摘Neurological disorders are still one of the major causes of death,and the vast need to find efficacious therapy is nowadays an essential goal of the scientific community.For Parkinson's disease(PD),amyotrophic lateral sclerosis(ALS),spinal cord injury,and intracerebral hemorrhage.
文摘Amyotrophic lateral sclerosis(ALS)is a highly aggressive adult-onset neurodegenerative disease caused by the progressive loss of upper and lower motor neurons.Clinically,it causes irreversible muscle atrophy and spasticity,leading to death due to respiratory failure,usually within 2–5 years after the first symptom onset.Approximately 85%of ALS cases are classified as sporadic,while the remaining 15%are of familial origin,but the overall clinical and molecular features of the disease are almost undistinguishable in the two forms.The majority of familial ALS cases are caused by pathogenic variants of C9orf72,SOD1,TARDBP,FUS,ANG and OPTN genes that are inherited by a Mendelian pattern and display high penetrance(Kiernan et al.,2020).
基金supported by Beyond Borders 2019(No.E84I20000580005)from Tor Vergata UniversityMIUR/PRIN 2017(No.2017A5TXC3)(MRC).
文摘Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease typically leading to death within 5 years from symptom onset. ALS familial forms are associated with mutations in several genes, including Superoxide Dismutase 1 (SOD1) and Fused in Sarcoma (FUS). Although genes linked to ALS participate in disparate biological processes, ALS genetic variants largely trigger shared pathogenic events such as oxidative stress, protein aggregation and defects in RNA processing. Moreover, ALS patients show systemic hypermetabolism that leads to increased energy expenditure at rest and thus weight loss during the disease course.1 ALS hypermetabolic phenotype and weight loss have been extensively characterized in mice bearing the G93A substitution in SOD1 protein (SOD1-G93A), which exhibit skeletal-muscle metabolic reprogramming before disease onset.
