Clinical genetic strategies for early onset neurodegenerative diseases

AbstractPurpose of reviewMethods for the genetic diagnosis of neurodegenerative disorders were reviewed, including their backgrounds and applications in the laboratory. Majority of disease-causing gene mutations were uncommon in the general population, where dominant variations could be easily identified in certain disorders. The development of molecular, next generation sequencing (NGS) and cytogenetic techniques allowed to identify multiple genetic mutations leading to diseases. Using of the accurate multivariate diagnosis of diseases would be essential for appropriate treatment of patients, genetic counseling and prevention strategiesRecent findingsAbnormal genes play an extremely important role in the pathogenesis of neurodegenerative disorders of the nervous system. Many studies of genetic have clearly indicated that the molecular mechanisms underlying the etiology and pathogenesis of most neurodegenerative disorders until now. Mutation is necessary for life, while fidelity is necessary for DNA replication. Mistakes in DNA replication/transcription can cause cells to produce either too much or too little protein or a defective protein. Studies on mutations have revealed the normal functions of genes, messages, proteins, the causes of many diseases, and the variability of responses among individuals. Based on the presence of damaging variants, there are many genes have identified that associated with neurodegenerative disorders through to genetic analyses of patients. Thi...
Source: Molecular and Cellular Toxicology - Category: Cytology Source Type: research

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Abstract Neurodegenerative proteinopathies are a group of pathologically similar, progressive disorders of the nervous system, characterised by structural alterations within and toxic misfolding of susceptible proteins. Oligomerisation of Aβ, tau, α-synuclein and TDP-43 leads to a toxin gain- or loss-of-function contributing to the phenotype observed in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. Misfolded proteins can adversely affect mitochondria, and post-mitotic neurones are especially sensitive to metabolic dysfunction. Misfolded proteins imp...
Source: Biochemical Society Transactions - Category: Biochemistry Authors: Tags: Biochem Soc Trans Source Type: research
AbstractThe advent of next-generation sequencing has changed genetic diagnostics, allowing clinicians to test concurrently for phenotypically overlapping conditions such as Alzheimer ’s disease (AD) and frontotemporal dementia (FTD). However, to interpret genetic results, clinicians require an understanding of the benefits and limitations of different genetic technologies, such as the inability to detect large repeat expansions in such diseases asC9orf72-associated FTD and amyotrophic lateral sclerosis. Other types of mutations such as large deletions or duplications and triple repeat expansions may also go undetecte...
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
Conclusions: [18F]FL2-b is a blood brain barrier permeable metal-protein aggregate binding agent. Autoradiography results from our previous work and the current study demonstrate increased uptake of the radiotracer in AD, ALS and DLB brain sections when compared to control brain sections. This data suggests to bind to metal-protein aggregates [18F]FL2-b in those diseases and further work is underway to evaluate its potential for estimating amyloid of TDP-43 aggregate burden and imaging disease progression in these neurodegenerative disorders. References: (1) Brooks, A.; Jackson, I.; Scott, P. J. Nucl. Med. 2017, 58 (supple...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Probes for Neuroimaging II Source Type: research
Conclusion: The complex molecular underpinnings of these disorders are currently elusive. Despite heterogeneous clinical and pathological expressions, common features have been recognized in many NDs which provide evidence of their convergence. PMID: 29755292 [PubMed]
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research
Authors: Liu X, Jiao B, Zhang W, Xiao T, Hou L, Pan C, Tang B, Shen L Abstract Recently, the coiled‑coil‑helix‑coiled‑coil‑helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
AbstractThe ability to reject an automatic tendency, i.e. inhibition, has been linked to the prefrontal cortex, but its neural underpinnings are still controversial. Neurodegenerative diseases represent an interesting model to explore this issue, given its frequent impairment in these disorders. We investigated the inhibitory impairment and its neural basis using four different tests, which evaluate the presence of inhibitory dysfunction (Stroop test, Hayling test, and two graphical perseveration tests), and assessed their correlation with brain metabolism using18F-fluorodeoxyglucose positron emission tomography in a group...
Source: Brain Imaging and Behavior - Category: Neurology Source Type: research
Abstract In a prospective study of dementia in Flanders (Belgium), we observed a substantial fraction of early-onset dementia patients who did not fulfill the criteria for a specific dementia subtype, leaving the patients without a precise clinical diagnosis. We selected 211 of these patients for genetic testing of causal genes linked to neurodegenerative brain diseases. In this group, the onset or inclusion age was 59.9 ± 8.2 years and 27.4% had a positive family history. We used a panel of 16 major genes linked to Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson'...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
go JL Abstract Aluminum (Al), a potentially neurotoxic element, provokes various adverse effects on human health such as dialysis dementia, osteomalacia, and microcytic anemia. It has been also associated with serious neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Parkinsonism dementia of Guam. The "aluminum hypothesis" of AD assumes that the metal complexes can potentiate the rate of aggregation of amyloid-β (Aβ), enhancing the toxicity of this peptide, and being able of contributing to the pathogenesis of AD. It has been supported by a number o...
Source: Biological Trace Element Research - Category: Biology Authors: Tags: Biol Trace Elem Res Source Type: research
AbstractNeurogranin (Ng) is a post-synaptic protein that previously has been shown to be a biomarker for synaptic function when measured in cerebrospinal fluid (CSF). The CSF concentration of Ng is increased in Alzheimer ’s disease dementia (ADD), and even in the pre-dementia stage. In this prospective study, we used an enzyme-linked immunosorbent assay that quantifies Ng in CSF to test the performance of Ng as a marker of synaptic function. In 915 patients, CSF Ng was evaluated across several different neurodege nerative diseases. Of these 915 patients, 116 had a neuropathologically confirmed definitive diagnos...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
Abstract Neurodegenerative diseases (NDDs) are incapacitating disorders that result in progressive motor and cognitive impairment. These disease include Alzheimer's disease the most common cause of dementia, frontotemporal dementia, amyotrophic lateral sclerosis, dementia with Lewy bodies, Parkinson's, Huntington's, Friedreich's ataxia, and prion disease. Dementia causing NDDs impose a high social and economic burden on communities around the world. Rapid growth in knowledge regarding the pathogenic mechanisms and disease-associated biomarkers of these diseases in the past few decades have accelerated the developm...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research
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