Open Access
of amyotrophic lateral sclerosis
John D. Lee,Nur A. Kamaruzaman,Jenny Nt Fung,Stephen Maxwell Taylor,Bradley J. Turner,Julie D. Atkin,Trent M. Woodruff,Peter G. Noakes +7 more
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TLDR
This Seminar summarises current concepts about the origin of the disease, what predisposes patients to develop the disorder, and why all cases of ALS are not the same.Abstract:
Background: Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1 G93A mice during defined disease stages. Methods: hSOD1 G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1 G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression. Results: We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1 G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death. Conclusions: These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1 G93A mouse. Hence, reducing complement-inducedread more
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Blood-Brain Barrier: From Physiology to Disease and Back
TL;DR: This review examines molecular and cellular mechanisms underlying the establishment of the blood-brain barrier, and examines how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders.
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C9orf72 nucleotide repeat structures initiate molecular cascades of disease
Aaron R. Haeusler,Christopher J. Donnelly,Goran Periz,Eric A J Simko,Patrick G. Shaw,Min-Sik Kim,Nicholas J. Maragakis,Juan C. Troncoso,Akhilesh Pandey,Rita Sattler,Jeffrey D. Rothstein,Jiou Wang +11 more
TL;DR: It is demonstrated that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provides the basis for a mechanistic model for repeat-associated neurodegenerative diseases.
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Stages of pTDP‐43 pathology in amyotrophic lateral sclerosis
Johannes Brettschneider,Kelly Del Tredici,Jon B. Toledo,John L. Robinson,David J. Irwin,Murray Grossman,EunRan Suh,Vivianna M. Van Deerlin,Elisabeth M. Wood,Young Min Baek,Linda K. Kwong,Edward B. Lee,Lauren Elman,Leo McCluskey,Lubin Fang,Simone Feldengut,Albert C. Ludolph,Virginia M.-Y. Lee,Heiko Braak,John Q. Trojanowski +19 more
TL;DR: To see whether the distribution patterns of phosphorylated 43kDa TAR DNA‐binding protein (pTDP‐43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition of neuropathological stages, a chiral model is constructed.
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13 reasons why the brain is susceptible to oxidative stress.
TL;DR: 13 reasons why the brain is susceptible to oxidative stress are rationalised and key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation.
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GDNF, NGF and BDNF as therapeutic options for neurodegeneration.
TL;DR: These neurotrophic factors are evaluated as potential short or long-term treatments, weighing up preclinical and clinical results with the possible effects on the underlying neurodegenerative process.
References
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Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
Image processing with ImageJ
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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Manuela Neumann,Deepak M. Sampathu,Linda K. Kwong,Adam C. Truax,Matthew Micsenyi,Thomas T. Chou,Jennifer Bruce,Theresa Schuck,Murray Grossman,Christopher M. Clark,Leo McCluskey,Bruce L. Miller,Eliezer Masliah,Ian R. A. Mackenzie,Howard Feldman,Wolfgang Feiden,Hans A. Kretzschmar,John Q. Trojanowski,Virginia M.-Y. Lee +18 more
TL;DR: It is shown that TDP-43 is the major disease protein in both frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis.
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Microglia: a sensor for pathological events in the CNS
TL;DR: An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.