Project description:This SuperSeries is composed of the following subset Series: GSE39642: NanoString nCounter immune-related gene expression in blood sorted CD14+CD16- monocytes from sALS, fALS and HC subjects GSE39643: NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects Refer to individual Series
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other
Project description:Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD.The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS-FTD.Missense changes were identified in an ALS-FTD patient (p.S120Y) and in a single case of limb onset sporadic ALS (p.T182M), although the pathogenicity of these variants remains unclear.PGRN mutations are not a common cause of ALS phenotypes.
Project description:Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS.
Project description:Identification of familial amyotrophic lateral sclerosis (fALS) related genes. Material from three hSOD1(G93A) transgenic mice was compared to material from three non-transgenic control mice using an alternating loop design on two-colour cDNA microarrays. Statistical data management and analysis: postgreSQL relational database (www.postgresql.org), Perl, and R (www.r-project.org); pin-wise lowess-regression based normalisation (Yang et al., 2002 [PMID: 11842121]); mixed ANOVA-model. Keywords = amyotrophic lateral sclerosis, ALS, SOD1 mouse model
Project description:Identification of familial amyotrophic lateral sclerosis (fALS) related genes. Material from three hSOD1(G93A) transgenic mice was compared to material from three non-transgenic control mice using an alternating loop design on two-colour cDNA microarrays. Statistical data management and analysis: postgreSQL relational database (www.postgresql.org), Perl, and R (www.r-project.org); pin-wise lowess-regression based normalisation (Yang et al., 2002 [PMID: 11842121]); mixed ANOVA-model. Keywords = amyotrophic lateral sclerosis, ALS, SOD1 mouse model Keywords: other
Project description:The clinical diagnosis of amyotrophic lateral sclerosis (ALS) relies on determination of progressive dysfunction of both cortical as well as spinal and bulbar motor neurons. However, the variable mix of upper and lower motor neuron signs result in the clinical heterogeneity of patients with ALS, resulting frequently in delay of diagnosis as well as difficulty in monitoring disease progression and treatment outcomes particularly in a clinical trial setting. As such, the present review provides an overview of recently developed novel non-invasive electrophysiological techniques that may serve as biomarkers to assess UMN and LMN dysfunction in ALS patients.
Project description:Our understanding of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is expanding rapidly as its genetic causes are uncovered. The pace of new gene discovery over the last 5 years has accelerated, providing new insights into the pathogenesis of disease and highlighting biological pathways as targets for therapeutic development. This article reviews our current understanding of the heritability of ALS and provides an overview of each of the major ALS genes, highlighting their phenotypic characteristics and frequencies as a guide for clinicians evaluating patients with ALS.
Project description:Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disorder of motor neurons that overlaps clinically with frontotemporal dementia (FTD). Investigations of the 10% of ALS cases that are transmitted as dominant traits have revealed numerous gene mutations and variants that either cause these disorders or influence their clinical phenotype. The evolving understanding of the genetic architecture of ALS has illuminated broad themes in the molecular pathophysiology of both familial and sporadic ALS and FTD. These central themes encompass disturbances of protein homeostasis, alterations in the biology of RNA binding proteins, and defects in cytoskeletal dynamics, as well as numerous downstream pathophysiological events. Together, these findings from ALS genetics provide new insight into therapies that target genetically distinct subsets of ALS and FTD.