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Motor neuron diseases, including amyotrophic lateral sclerosis (ALS), are devastating disorders and effective therapies have not yet been established. One of the reasons for this lack of therapeutics, especially in sporadic ALS (SALS), is attributed to the absence of excellent disease models reflecting its pathology. For this purpose, identifying important key molecules for ALS pathomechanisms and developing disease models is crucial, and omics approaches, including genomics, transcriptomics and proteomics, have been employed. In particular, transcriptome analysis using cDNA microarray is the most popular omics approach and we have previously identified dynactin-1 as an important molecule downregulated in the motor neurons of SALS patients from the early stage of the disease. Dynactin-1 is also known as a causative gene in familial ALS (FALS). Dynactin-1 is a major component of the dynein/dynactin motor protein complex functioning in retrograde axonal transport. In motor neuron diseases as well as other neurodegenerative diseases, the role of axonal transport dysfunction in their pathogenesis always draws attention, but its precise mechanisms remain to be fully elucidated. In this article, we review our previous omics approach to SALS and the role of dynactin-1 in the pathogenesis of ALS. Finally, we emphasize the need for creating novel SALS disease models based on the results of omics analysis, especially based on the observation that dynactin-1 gene expression was downregulated in SALS motor neurons.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya Department of Speech Pathology and Audiology, Aichi Gakuin University School of Health Science, Aichi Core Research for Evolutional Science and Technolo
This article was published in the following journal.
Name: Neuropathology : official journal of the Japanese Society of Neuropathology
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Progressive muscular atrophy (PMA), or the lower motor neuron disease, is a sporadic disorder characterized by onset in adulthood, pure lower motor neuron involvement and relatively benign course. Mus...
The involvement of upper motor neuron (UMN) degeneration is crucial to the diagnosis of amyotrophic lateral sclerosis (ALS). However, it is difficult to detect in the early stages, and particularly wi...
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Direct gene delivery to the neurons of interest, without affecting other neuron populations in the cerebral cortex, represent a challenge due to the heterogeneity and cellular complexity of the brain....
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a ...
Levetiracetam (Keppra) is used to treat partial onset seizures. Its biological effects suggest it might also be useful in treating 3 aspects of human motor neuron diseases (MNDs) for whic...
This study will collect blood samples from patients with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) to be used for research on genetic causes of motor neuron d...
The purpose of this study is to learn about rates of patient-reported disease progression in patients with motor neuron diseases (amyotrophic lateral sclerosis, progressive muscular atroph...
Despite significant progress in the identification of mechanisms involved in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS) and other motor system diseases, the actual pa...
Complete or severe weakness of the muscles of respiration. This condition may be associated with MOTOR NEURON DISEASES; PERIPHERAL NERVE DISEASES; NEUROMUSCULAR JUNCTION DISEASES; SPINAL CORD DISEASES; injury to the PHRENIC NERVE; and other disorders.
A SMN complex protein that is closely-related to SURVIVAL OF MOTOR NEURON 1 PROTEIN. In humans, the protein is encoded by an often duplicated gene found near the inversion centromere of a large inverted region of CHROMOSOME 5.
A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.
Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations can often by visualized and take the form of a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294)
A SMN complex protein that is essential for the function of the SMN protein complex. In humans the protein is encoded by a single gene found near the inversion telomere of a large inverted region of CHROMOSOME 5. Mutations in the gene coding for survival of motor neuron 1 protein may result in SPINAL MUSCULAR ATROPHIES OF CHILDHOOD.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...