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Motor neuron diseases or motor neurone diseases (MNDs) are a group of rare neurodegenerative disorders that selectively affect motor neurons, the cells which control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy (PBP), pseudobulbar palsy, progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), spinal muscular atrophy (SMA) and monomelic amyotrophy (MMA), as well as some rarer variants resembling ALS.
Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as behavioral or language disorders with gradual onsets. The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Pick's disease, and two variants of primary progressive aphasia – semantic variant (svPPA), and nonfluent variant (nfvPPA). Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include corticobasal syndrome and FTD with amyotrophic lateral sclerosis (ALS) FTD-ALS also called FTD-MND.
Primary lateral sclerosis (PLS) is a very rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor neuron diseases. Motor neuron diseases develop when the nerve cells that control voluntary muscle movement degenerate and die, causing weakness in the muscles they control.
Progressive muscular atrophy (PMA), also called Duchenne–Aran disease and Duchenne–Aran muscular atrophy, is a disorder characterised by the degeneration of lower motor neurons, resulting in generalised, progressive loss of muscle function.
Distal myopathy is a group of rare genetic disorders that cause muscle damage and weakness, predominantly in the hands and/or feet. Mutation of many different genes can be causative. Many types involve dysferlin.
Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, familial amyotrophic lateral sclerosis and Parkinson's disease.
Alsin is a protein that in humans is encoded by the ALS2 gene. ALS2 orthologs have been identified in all mammals for which complete genome data are available.
Matrin-3 is a protein that in humans is encoded by the MATR3 gene.
Serine palmitoyltransferase, long chain base subunit 1, also known as SPTLC1, is a protein which in humans is encoded by the SPTLC1 gene.
Kinesin heavy chain isoform 5A is a protein that in humans is encoded by the KIF5A gene.
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common type of motor neuron disease. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty speaking or swallowing. Half of the people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Most people experience pain. The affected muscles are responsible for chewing food, speaking, and walking. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. ALS eventually causes paralysis and early death, usually from respiratory failure.
C9orf72 is a protein which in humans is encoded by the gene C9orf72.
Multisystem proteinopathy (MSP) is a dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone, and/or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), inclusion body myopathy (IBM), Paget's disease of bone (PDB), or as a combination of these disorders. Historically, several different names have been used to describe MSP, most commonly "inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD)" or "inclusion body myopathy with frontotemporal dementia, Paget's disease of bone, and amyotrophic lateral sclerosis (IBMPFD/ALS)." However, IBMPFD and IBMPFD/ALS are now considered outdated classifications and are more properly referred to as MSP, as the disease is clinically heterogeneous and its phenotypic spectrum extends beyond IBM, PDB, FTD, and ALS to include motor neuron disease, Parkinson's disease features, and ataxia features. Although MSP is rare, growing interest in this syndrome derives from the molecular insights the condition provides into the etiological relationship between common age-related degenerative diseases of muscle, bone, and brain.
Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial, also known as Protein N27C7-4 is a protein that in humans is encoded by the CHCHD10 gene.
Unc-13 homolog A is a protein that in humans is encoded by the UNC13A gene.
Manoj Kumar Jaiswal is an Indian-American neuroscientist working at Turn Biotechnologist Inc. as a Senior Scientist, a Drug Discovery Company in Sunnyvale, San Fransisco. He is working towards mRNA Therapeutics, Next Generation Sequencing, Human Disease Modeling and Cellular Reprogramming. He was a full-time non tenure track faculty in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai from 2017 until 2022. He is well known for his contributions to Motor Neuron Disease, ALS and Dementia and in particular finding the first evidence of disrupted Ca2+ homeostasis and oxidative stress induced by reactive oxygen species in SOD1G93A mouse model and mtSOD1 cell culture model of ALS. His research areas include neurodegeneration and rare diseases as well as single cell sequencing, multi-omics, spatial transcriptomics, and optical imaging. Using next-generation sequencing such as single-nucleus RNA sequencing (snRNA-seq) and Assay for Transposase-Accessible Chromatin using sequencing (snATAC-seq), along with epigenome (ChIP-Seq), and 3D genome (Hi-C) study in fluorescence-activated nuclei sorting (FANS)-sorted cell-type-specific populations of five major cell types, Dr. Jaiswal uncover novel cell-type-specific alterations in the transcriptome and epigenome of human autopsy brain [samples] associated with C9orf72 ALS (C9-ALS) and C9-FTD mutations in Human patients. He characterize the effect of genetic variation on the cellular architecture, and shed light on the 1) complex pathophysiological mechanisms regulating gene expression in diseased cells, 2) cell-type-specific epigenetic impact on disease, and 3) 3D configuration of the diseased brain genome architecture. He is the member of editorial board of several scientific journals, adhoc grant reviewer for Medical Research Council, European Science Foundation, Research Foundation of The City University of New York and Neuroonline Community Leader of Society for Neuroscience.
Amyotrophic Lateral Sclerosis (ALS), is a neurodegenerative disease that typically affects adults around 54-67 years of age, although anyone can be diagnosed with the disease. People diagnosed with ALS live on average 2–4 years after diagnosis due to the quick progression of the disease. The progression and severity of ALS is rated by doctors on the ALS Functional Rating Scale, which has been revised and is referred to as ALSFRS-R.
There are more than 25 genes known to be associated with amyotrophic lateral sclerosis (ALS) as of June 2018, which collectively account for about 70% of cases of familial ALS (fALS) and 10% of cases of sporadic ALS (sALS). About 5–10% of cases of ALS are directly inherited from a person's parents. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance, meaning that mutations in two or more genes are required to cause disease.
Research on amyotrophic lateral sclerosis has focused on animal models of the disease, its mechanisms, ways to diagnose and track it, and treatments.
Merit Cudkowicz is an American neurologist, neuroscientist, and studies amyotrophic lateral sclerosis (ALS). Cudkowicz is Julieanne Dorn Professor of Neurology at Harvard Medical School, director of the ALS clinic and the Neurological Clinical Research Institute at Massachusetts General Hospital (MGH) and chair of the Department of Neurology at MGH. Cudkowicz has led several large scale collaborations and clinical trials to test novel treatments for ALS and as of 2020 researches ways to detect early biomarkers of ALS to improve diagnosis.
References
- ↑ "Neuromuscular Diseases Research Section". National Institute on Aging. Retrieved 2019-03-26.
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- ↑ Johnson, Janel O.; Mandrioli, Jessica; Benatar, Michael; Abramzon, Yevgeniya; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Gibbs, J. Raphael; Brunetti, Maura; Gronka, Susan; Wuu, Joanne; Ding, Jinhui; McCluskey, Leo; Martinez-Lage, Maria; Falcone, Dana; Hernandez, Dena G.; Arepalli, Sampath; Chong, Sean; Schymick, Jennifer C.; Rothstein, Jeffrey; Landi, Francesco; Wang, Yong-Dong; Calvo, Andrea; Mora, Gabriele; Sabatelli, Mario; Monsurrò, Maria Rosaria; Battistini, Stefania; Salvi, Fabrizio; Spataro, Rossella; Sola, Patrizia; Borghero, Giuseppe; Galassi, Giuliana; Scholz, Sonja W.; Taylor, J. Paul; Restagno, Gabriella; Chiò, Adriano; Traynor, Bryan J. (2010). "Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS". Neuron. 68 (5): 857–864. doi:10.1016/j.neuron.2010.11.036. ISSN 0896-6273. PMC 3032425 . PMID 21145000.
- ↑ Johnson, Janel O; Pioro, Erik P; Boehringer, Ashley; Chia, Ruth; Feit, Howard; Renton, Alan E; Pliner, Hannah A; Abramzon, Yevgeniya; Marangi, Giuseppe; Winborn, Brett J; Gibbs, J Raphael; Nalls, Michael A; Morgan, Sarah; Shoai, Maryam; Hardy, John; Pittman, Alan; Orrell, Richard W; Malaspina, Andrea; Sidle, Katie C; Fratta, Pietro; Harms, Matthew B; Baloh, Robert H; Pestronk, Alan; Weihl, Conrad C; Rogaeva, Ekaterina; Zinman, Lorne; Drory, Vivian E; Borghero, Giuseppe; Mora, Gabriele; Calvo, Andrea; Rothstein, Jeffrey D; Drepper, Carsten; Sendtner, Michael; Singleton, Andrew B; Taylor, J Paul; Cookson, Mark R; Restagno, Gabriella; Sabatelli, Mario; Bowser, Robert; Chiò, Adriano; Traynor, Bryan J (2014). "Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis". Nature Neuroscience. 17 (5): 664–666. doi:10.1038/nn.3688. ISSN 1097-6256. PMC 4000579 . PMID 24686783.
- ↑ Nicolas, Aude; Kenna, Kevin P.; Renton, Alan E.; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A.; Kenna, Brendan J.; Nalls, Mike A.; Keagle, Pamela; Rivera, Alberto M. (2018). "Genome-wide Analyses Identify KIF5A as a Novel ALS Gene". Neuron. 97 (6): 1268–1283.e6. doi:10.1016/j.neuron.2018.02.027. ISSN 1097-4199. PMC 5867896 . PMID 29566793.
- ↑ Dewan, Ramita; Chia, Ruth; Ding, Jinhui; Hickman, Richard A.; Stein, Thor D.; Abramzon, Yevgeniya; Ahmed, Sarah; Sabir, Marya S.; Portley, Makayla K.; Tucci, Arianna; Ibáñez, Kristina (2021). "Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis". Neuron. 109 (3): 448–460.e4. doi:10.1016/j.neuron.2020.11.005. ISSN 1097-4199. PMC 7864894 . PMID 33242422.
- ↑ Johnson, Janel O.; Chia, Ruth; Miller, Danny E.; Li, Rachel; Kumaran, Ravindran; Abramzon, Yevgeniya; Alahmady, Nada; Renton, Alan E.; Topp, Simon D.; Gibbs, J. Raphael; Cookson, Mark R.; Sabir, Marya S.; Dalgard, Clifton L.; Troakes, Claire; Jones, Ashley R. (2021-10-01). "Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis". JAMA Neurology. 78 (10): 1236–1248. doi:10.1001/jamaneurol.2021.2598. ISSN 2168-6157. PMC 8406220 . PMID 34459874.
- ↑ "Derek Denny-Brown Neurological Scholar Award | American Neurological Association (ANA)". myana.org. Retrieved 2019-03-26.
- ↑ "Wings Over Wall Street - Awards". wingsoverwallstreet.org. Retrieved 2019-03-26.
- ↑ "ALS Association".
- ↑ "American Academy of Neurology".
- ↑ "Amyotrophic Lateral Sclerosis Research Program, Programmatic Panels; Congressionally Directed Medical Research Programs". cdmrp.army.mil. Retrieved 2019-03-26.
