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A neurodegenerative disease is caused by the progressive loss of neurons,in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis,multiple sclerosis,Parkinson's disease,Alzheimer's disease,Huntington's disease,multiple system atrophy,tauopathies,and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry,ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons,these diseases are considered to be incurable;however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level,including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes,called PSEN1 that codes for presenilin 1 (PS-1) and PSEN2 that codes for presenilin 2 (PS-2). Both genes show conservation between species,with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar,sel-12 and hop-1.
Sortilin-related receptor,L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.
Nicastrin,also known as NCSTN,is a protein that in humans is encoded by the NCSTN gene.
APH-1 is a protein originally identified in the round worm Caenorhabditis elegans as a regulator of the cell-surface localization of nicastrin in the Notch signaling pathway.
Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex,which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.
Presenilin-2 is a protein that is encoded by the PSEN2 gene.
Early-onset Alzheimer's disease (EOAD),also called younger-onset Alzheimer's disease (YOAD),is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's,accounting for only 5–10% of all Alzheimer's cases. About 60% have a positive family history of Alzheimer's and 13% of them are inherited in an autosomal dominant manner. Most cases of early-onset Alzheimer's share the same traits as the "late-onset" form and are not caused by known genetic mutations. Little is understood about how it starts.
Andrew B. Singleton is a British neurogeneticist currently working in the USA. He was born in Guernsey,the Channel Islands in 1972,where he lived until he was 18 years old. His secondary education was conducted at the Guernsey Grammar School. He earned a first class degree in Applied Physiology from Sunderland University and his PhD in neuroscience from the University of Newcastle upon Tyne where he studied the genetics of Alzheimer's disease and other dementias at the Medical Research Council (MRC) Neurochemical Pathology Unit. He moved to the United States in 1999,where he began working at the Mayo Clinic in Jacksonville,Florida studying the genetic basis of Parkinson's disease,ataxia,and dystonia. He moved to the National Institutes of Health in 2001 to head the newly formed Molecular Genetics unit within the Laboratory of Neurogenetics. In 2006 he took over as Chief of the Laboratory of Neurogenetics and became an NIH Distinguished Investigator in the intramural program at the National Institute on Aging (NIA) in 2017. In 2020 he stepped down as the Chief of the Laboratory of Neurogenetics and became the Acting Director of the newly formed Center for Alzheimer's and Related Dementias at the NIA. In 2021 he became the Director of CARD.
Rudolph Emile 'Rudy' Tanzi a professor of Neurology at Harvard University,vice-chair of neurology,director of the Genetics and Aging Research Unit,and co-director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH).
C9orf72 is a protein which in humans is encoded by the gene C9orf72.
The Krembil Research Institute,formerly known as the Toronto Western Research Institute,is an academic medical research institute in Toronto. It is one of the largest research institutes in Canada focusing on human neurological disease.
Alison Mary Goate is the Jean C. and James W. Crystal Professor and Chair of the Department of Genetics and Genomic Sciences and Director of the Loeb Center for Alzheimer's Disease at Icahn School of Medicine at Mount Sinai,New York City. She was previously professor of genetics in psychiatry,professor of genetics,and professor of neurology at Washington University School of Medicine.
Bryan J. Traynor is a neurologist and a senior investigator at the National Institute on Aging,and an adjunct professor at Johns Hopkins University. Dr. Traynor studies the genetics of human neurological conditions such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). He led the international consortium that identified pathogenic repeat expansions in the C9orf72 gene as a common cause of ALS and FTD. Dr. Traynor also led efforts that identified other Mendelian genes responsible for familial ALS and dementia,including VCP,MATR3,KIF5A,HTT,and SPTLC1.
Donald Lowell Price was an American neuropathologist and professor at the Johns Hopkins School of Medicine. His research aimed to understand the molecular basis of neurodegenerative diseases,particularly Alzheimer's disease. Price received a number of awards for his work and served as the President of both the American Association of Neuropathologists and the Society for Neuroscience.
Rosa Rademakers is a Dutch neurogeneticist and professor within the Department of Neuroscience at the Mayo Clinic. Her research centers on the genetic basis of neurodegenerative diseases,such as identifying causal genes and their function,exploring familial risk factors,and the mechanism of the degeneration. Her neurodegenerative diseases of focus include "Alzheimer's disease (AD),frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)." She received a Bachelor of Arts in Biology,a Master of Arts in Biochemistry,and a Ph.D. in Science,all from the University of Antwerp. Originally from the Netherlands,she came to the Mayo Clinic in 2005 for a post-doctoral fellowship,and in 2007 she was given a lab director position.
Carlos Cruchaga is a human genomicist with expertise in multi-omics,informatics,and neurodegeneration,with a focus on Alzheimer's and Parkinson's Disease. He is a Professor of Psychiatry,Neurology and Genetics and Washington University School of Medicine. He is founding director of the Neurogenomics and Informatic (NGI) center at Washington University School of Medicine.
Martin Neil Rossor is a British clinical neurologist with a specialty interest in degenerative dementias and familial disease.
Gerard David Schellenberg is an academic neuropathologist who specializes in the research of Alzheimer's disease. He is the director of Penn Neurodegeneration Genomics Center as well as a professor of Pathology and Laboratory Medicine at the University of Pennsylvania. He is a leading contributor to Alzheimer's disease research.
Alzheimer's disease (AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as Hispanics and Latinos are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease,characterized by the presence of amyloid-beta plaques and neurofibrillary tangles,that causes memory loss and cognitive decline in its patients. However,pathology and symptoms have been shown to manifest differently in Hispanic/Latinos,as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally,there is a large genetic component of AD,with mutations in the amyloid precursor protein (APP),apolipoprotein E APOE),presenilin 1 (PSEN1),bridging Integrator 1 (BIN1),SORL1,and clusterin (CLU) genes increasing one's risk to develop the condition. However,research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally,this population experiences higher rates of comorbidities,that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors,such as low income and a language barrier,that affect their ability to engage in clinical trials and receive proper care.
References
- ↑ "Science.ca : Peter Henry St. George-Hyslop".
- ↑ "Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer Disease". Nature.
- ↑ "Nicastrin modulates presenilin-mediated Notch/Gip1 signal transduction and bAPP processing". Nature.
- ↑ Guerreiro, R.; Wojtas, A.; Bras, J.; Carrasquillo, M.; Rogaeva, E.; Majounie, E.; Cruchaga, C.; Sassi, C.; Kauwe, J. S.; Younkin, S.; Hazrati, L.; Collinge, J.; Pocock, J.; Lashley, T.; Williams, J.; Lambert, J. C.; Amouyel, P.; Goate, A.; Rademakers, R.; Morgan, K.; Powell, J.; St. George-Hyslop, P.; Singleton, A.; Hardy, J.; The Alzheimer Genetic Analysis Group (2012). "TREM2 variants in Alzheimer's disease". New England Journal of Medicine. 368 (2): 117–127. doi:10.1056/NEJMoa1211851. PMC 3631573 . PMID 23150934.
- ↑ "Association of Apoliprotein E allele e4 with the late-onset familial and sporadic Alzheimer Disease". Neurology.
- ↑ Rogaeva, E.; et al. (2007). "The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer's Disease". Nature Genetics. 39 (2): 168–177. doi:10.1038/ng1943. PMC 2657343 . PMID 17220890.
- ↑ Hernandez-Sapiens, M. A.; Reza-Zaldívar, E. E.; Márquez-Aguirre, A. L.; Gómez-Pinedo, U.; Matias-Guiu, J.; Cevallos, R. R.; Mateos-Díaz, J. C.; Sánchez-González, V. J.; Canales-Aguirre, A. A. (2022). "Presenilin mutations and their impact on neuronal differentiation in Alzheimer's disease". Neural Regeneration Research. 17 (1): 31–37. doi: 10.4103/1673-5374.313016 . PMC 8451546 . PMID 34100423.
- ↑ Hardy, J. (2006). "A Hundred Years of Alzheimer's Disease Research". Neuron. 52 (1): 3–13. doi:10.1016/j.neuron.2006.09.016. PMID 17015223.
- ↑ "Horizons magazine". 19 February 2013.
- ↑ "Prof Peter St George-Hyslop". www.cimr.cam.ac.uk. Archived from the original on 2007-11-09.
- ↑ "About the Centre | Tanz Centre for Research in Neurodegenerative Diseases".
- ↑ "Director's Message | Tanz Centre for Research in Neurodegenerative Diseases". tanz.med.utoronto.ca.
- ↑ "MetLife Foundation Awards for Medical Research in Alzheimer's Disease" (PDF). Archived from the original (PDF) on 13 October 2018.
- ↑ "Dan David Foundation announces winners of prize". The Jerusalem Post | JPost.com. 11 February 2014. Retrieved 2020-11-02.
- ↑ "Order of Canada Appointments". 29 June 2018. Archived from the original on 29 September 2020. Retrieved 18 February 2019.
