Abstract:
:He spent tens of thousands of hours peering through the oculars of a microscope at stained brain tissue sections from thousands of patients who died with or without a neurodegenerative disorder; most of those patients he had himself cared for and had removed and processed their brain tissues upon their death. His discerning mind, humble demeanor, optimism and patience were fundamental features of his character. Through his research discoveries and advocacy, Dr. William R. Markesbery fought for those millions of elderly Americans with Alzheimer's disease (AD) and their families and friends. For over a decade, my laboratory was located directly above Dr. Markesbery's in the Sanders-Brown Research Center on Aging at the University of Kentucky in Lexington. In this article, I first provide several examples of how he moved research on AD forward on multiple fronts, not only by building one of the best AD Research Centers in the world, but also by providing a helping hand to the tens of thousands of Kentuckian's and their families to ease their suffering as best he could. Also described below are the results of several research projects on which I had the good fortune of collaborating with Dr. Markesbery.
journal_name
Neuromolecular Medjournal_title
Neuromolecular medicineauthors
Mattson MPdoi
10.1007/s12017-010-8124-8subject
Has Abstractpub_date
2011-03-01 00:00:00pages
6-10issue
1eissn
1535-1084issn
1559-1174journal_volume
13pub_type
传,历史文章,杂志文章abstract::The metabolic syndrome is characterized by the clustering of various common metabolic abnormalities in an individual and it is associated with increased risk for the development of type 2 diabetes and cardiovascular diseases. Its prevalence in the general population is approximately 25%. Central fat accumulation and i...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8022-5
更新日期:2008-01-01 00:00:00
abstract::Adenosine A2A receptor (A2AR) is a G-protein-coupled receptor highly expressed in basal ganglia. Its expression levels are severely reduced in Huntington's disease (HD), and several pharmacological therapies have shown its implication in this neurodegenerative disorder. The main goal of this study was to gain insight ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-013-8219-0
更新日期:2013-06-01 00:00:00
abstract::The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-cat...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:5:2:133
更新日期:2004-01-01 00:00:00
abstract::The original version of this article unfortunately contained a mistake. Gary S. Laco should not be listed as an author in the author group. ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,已发布勘误
doi:10.1007/s12017-020-08593-4
更新日期:2020-06-01 00:00:00
abstract::Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-016-8414-x
更新日期:2016-09-01 00:00:00
abstract::Clathrin assembly proteins AP180 and CALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse. Although studies using several invertebrate model systems have indicated a role for AP180 in SV recycl...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-012-8194-x
更新日期:2013-03-01 00:00:00
abstract::Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodeg...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8053-y
更新日期:2008-01-01 00:00:00
abstract::Parkinson's disease (PD) features oxidative stress and accumulation of misfolded (unfolded, alternatively folded, or mutant) proteins with associated loss of dopaminergic neurons. Oxidative stress and the accumulated misfolded proteins elicit cellular responses that include an endoplasmic reticulum (ER) stress respons...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-008-8047-9
更新日期:2008-01-01 00:00:00
abstract::Neurons and especially their synapses often project long thin processes that can invaginate neighboring neuronal or glial cells. These "invaginating projections" can occur in almost any combination of postsynaptic, presynaptic, and glial processes. Invaginating projections provide a precise mechanism for one neuron to...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-015-8358-6
更新日期:2015-09-01 00:00:00
abstract::Abnormal interactions and misfolding of synaptic proteins in the nervous system are being extensively explored as important pathogenic events resulting in neurodegeneration in various neurological disorders. These include Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). In AD, m...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:4:1-2:21
更新日期:2003-01-01 00:00:00
abstract::Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenz...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8508-8
更新日期:2019-06-01 00:00:00
abstract::Parkinson's disease (PD) is the most common neurodegenerative motor disorder, marked by chronic progressive loss of neurons in the substantia nigra, thereby damaging purposeful control of movement. For decades, it was believed that PD was caused solely by environmental causes. However, the discovery of genetic factors...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:1:2:95
更新日期:2002-01-01 00:00:00
abstract::In addition to myelin loss and oligodendrocyte injury, axonal damage is a major cause of irreversible neurological disability in multiple sclerosis (MS). A series of studies have demonstrated that Rho kinase (ROCK) is involved in synaptic plasticity of neurons. Here, we found that ROCK activity in MS serum was elevate...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-015-8374-6
更新日期:2015-12-01 00:00:00
abstract::Epileptic seizures have long been recognised as a complication of the clinical syndrome of Alzheimer's disease, particularly in advanced disease, but have hitherto been viewed essentially as epiphenomena of the neurodegenerative process. Progress with animal models of Alzheimer's disease has suggested that this view m...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-009-8076-z
更新日期:2010-03-01 00:00:00
abstract::Mitochondria are key cytoplasmic organelles, responsible for generating cellular energy, regulating intracellular calcium levels, altering the reduction-oxidation potential of cells, and regulating cell death. Increasing evidence suggests that mitochondria play a central role in aging and in neurodegenerative diseases...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-008-8044-z
更新日期:2008-01-01 00:00:00
abstract::Selective degeneration and death of motor neurons in SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS) is accompanied by axonal disorganization and reduced slow axonal transport in the three most frequently used mouse models of mutant SOD1-mediated ALS. To test whether suppression of axonal degeneration (freque...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1385/NMM:5:3:193
更新日期:2004-01-01 00:00:00
abstract::Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manifestations of ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-007-8019-5
更新日期:2008-01-01 00:00:00
abstract::Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor sympto...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8499-5
更新日期:2018-09-01 00:00:00
abstract::Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-017-8464-8
更新日期:2017-12-01 00:00:00
abstract::Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-016-8415-9
更新日期:2017-03-01 00:00:00
abstract::The α-synuclein gene (SNCA) plays a major role in the aetiology of Lewy body disease (LBD) including Parkinson's disease (PD). Point mutations and genetic alterations causing elevated gene expression are causally linked to familial PD. To what extent epigenetic changes play a role in the regulation of α-synuclein expr...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-011-8163-9
更新日期:2011-12-01 00:00:00
abstract::Reperfusion after cerebral ischemia causes additional ischemic injuries due to sudden recovery of blood supply. It usually produces excessive reactive species, mitochondrial dysfunction, oxidative stress, and cell apoptosis. Our study is designed to examine the role of miR-421 antagomir in cerebral ischemia/reperfusio...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-020-08600-8
更新日期:2020-09-01 00:00:00
abstract::Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-016-8399-5
更新日期:2016-12-01 00:00:00
abstract::There is evidence that chronic hyponatremia, even when mild, may cause neurological signs and symptoms. These have been traditionally associated with water movement into nervous cells, as a result of the hypotonic state. The aim of the present study was to determine whether low extracellular sodium directly exerts neg...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-013-8235-0
更新日期:2013-09-01 00:00:00
abstract::Functional electrical stimulation (FES) has been widely adopted to elicit muscle contraction in rehabilitation training after spinal cord injury (SCI). Conventional FES modalities include stimulations coupled with rowing, cycling, assisted walking and other derivatives. In this review, we studied thirteen clinical rep...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1007/s12017-019-08589-9
更新日期:2020-12-01 00:00:00
abstract::It is an established fact that orexin plays an important role in regulating the reproductive axis and the secretions of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular mechanisms are not fully recognized. Accordingly, the aim of the present study is to find o...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8506-x
更新日期:2018-12-01 00:00:00
abstract::The X-linked form of Charcot-Marie-Tooth disease (CMT1X) is the second most common molecularly designated form of hereditary motor and sensory neuropathy. The clinical phenotype is characterized by progressive distal muscle atrophy and weakness, areflexia, and variable sensory abnormalities. Affected males have modera...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/nmm:8:1-2:107
更新日期:2006-01-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons and descending motor tracts of the CNS. We have evaluated the CNS of a murine model of familial ALS based on the over-expression of mutant human superoxide dismutase (mSOD; G93A) using magnetic resonance microscopy ...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-007-8002-1
更新日期:2007-01-01 00:00:00
abstract::Neurodegeneration is the main pathological correlate of accumulating disability in progressive stages of Multiple Sclerosis (MS), but both histologic and imaging studies detect significant tissue loss even in early disease. These observations raise the question as to whether neurodegeneration in MS is a primary mechan...
journal_title:Neuromolecular medicine
pub_type: 杂志文章,评审
doi:10.1385/NMM:3:3:147
更新日期:2003-01-01 00:00:00
abstract::Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine metabolism. Elevated plasma Hcy levels (> 15 µM) result in a condition called hyperhomocysteinemia (HHcy), which is an independent risk factor in the development of various neurodegenerative disorders. Reactive oxygen species (ROS) produced b...
journal_title:Neuromolecular medicine
pub_type: 杂志文章
doi:10.1007/s12017-018-8505-y
更新日期:2018-12-01 00:00:00