scholarly journals A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele

2015 ◽  
Vol 35 (21) ◽  
pp. 8091-8106 ◽  
Author(s):  
M. Praggastis ◽  
B. Tortelli ◽  
J. Zhang ◽  
H. Fujiwara ◽  
R. Sidhu ◽  
...  
2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Adrián Cortés Sanchón ◽  
Harshitha Santhosh Kumar ◽  
Matilde Mantovani ◽  
Ivan Osinnii ◽  
José María Mateos ◽  
...  

AbstractProteostasis is a challenge for cellular organisms, as all known protein synthesis machineries are error-prone. Here we show by cell fractionation and microscopy studies that misfolded proteins formed in the endoplasmic reticulum can become associated with and partly transported into mitochondria, resulting in impaired mitochondrial function. Blocking the endoplasmic reticulum-mitochondria encounter structure (ERMES), but not the mitochondrial sorting and assembly machinery (SAM) or the mitochondrial surveillance pathway components Msp1 and Vms1, abrogated mitochondrial sequestration of ER-misfolded proteins. We term this mitochondria-associated proteostatic mechanism for ER-misfolded proteins ERAMS (ER-associated mitochondrial sequestration). We testify to the relevance of this pathway by using mutant α-1-antitrypsin as an example of a human disease-related misfolded ER protein, and we hypothesize that ERAMS plays a role in pathological features such as mitochondrial dysfunction.


Author(s):  
David Baglietto-Vargas ◽  
Rahasson R. Ager ◽  
Rodrigo Medeiros ◽  
Frank M. LaFerla

The incidence and prevalence of neurodegenerative disorders (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), etc.) are growing rapidly due to increasing life expectancy. Researchers over the past two decades have focused their efforts on the development of animal models to dissect the molecular mechanisms underlying neurodegenerative disorders. Existing models, however, do not fully replicate the symptomatic and pathological features of human diseases. This chapter focuses on animal models of AD, as this disorder is the most prevalent of the brain degenerative conditions afflicting society. In particular, it briefly discusses the current leading animal models, the translational relevance of the preclinical studies using such models, and the limitations and shortcomings of using animals to model human disease. It concludes with a discussion of potential means to improve future models to better recapitulate human conditions.


2010 ◽  
Vol 20 (4) ◽  
pp. 806-819 ◽  
Author(s):  
Cheryl Jacobs ◽  
Ying Huang ◽  
Tehmina Masud ◽  
William Lu ◽  
Gerwin Westfield ◽  
...  

Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.


Author(s):  
D.J. Meyerhoff

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),


2007 ◽  
Vol 177 (4S) ◽  
pp. 158-158
Author(s):  
Nicolas B. Delongchamps ◽  
Vishal Chandan ◽  
Richard Jones ◽  
Gregory Threatte ◽  
Mary Jumbelic ◽  
...  

VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Grotenhermen

Background: To investigate the hypothesis that cases of arteritis similar to thromboangiitis obliterans (TAO) and associated with the use of cannabis were caused by cannabis or THC (dronabinol), or that cannabis use is a co-factor of TAO. Patients and methods: A systematic review on case reports and the literature on so-called cannabis arteritis, TAO, and cardiovascular effects of cannabinoids was conducted. Results: Fifteen reports with 57 cases of an arteritis associated with the use of cannabis and two additional case series of TAO, in which some patients also used cannabis, were identified. Clinical and pathological features of cannabis-associated arteritis do not differ from TAO and the major risk factor of TAO, tobacco use, was present in most, if not in all of these cases. The proposed pathophysiological mechanisms for the development of an arteritis by cannabis use are not substantiated. Conclusions: The hypothesis of cannabis being a causative factor or co-factor of TAO or an arteritis similar to TAO is not supported by the available evidence. The use of the term “cannabis arteritis” should be avoided until or unless more convincing scientific support is forthcoming.


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