Vol 1-3 Mini Review

Oleic Acid and Cholinergic dysfunction in Down Syndrome Models of the Central Nervous System

Ana Velasco* and Maruan Hijazi

Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Spain

Down syndrome (DS): or trisomy 21: is the most common autosomal aneuploidy and the leading genetic cause of intellectual disability. It is widely established that mental retardation is primarily a consequence of brain functioning and developmental abnormalities in neurogenesis. Some changes in the physical structure of the dendrites are a major cause of impaired synaptic plasticity of DS. The overexpression of the dual specificyty tyrsone phosphorylation-regulated kinase 1A (DYRK1A): located on chromosome 21: is involved in cellular plasticity and responsible for central nervous system disturbance in DS.

Oleic acid is a neurotrophic factor that promotes neuronal differentiation and increases the levels of choline acetyltransferase (ChAT). Furthermore: it has recently been shown that it induces migration and formation of new synapses in euploid cells. However: remarkably oleic acid fails to reproduce the same effects in trisomic cells.

Here we review the hypothesis that oleic acid-dependent synaptic plasticity may be dependent on the lipid environment. Thus: differences in membrane composition may be essential to understand why oleic acid promotes higher cell plasticity in euploid than in trisomic cells.

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Vol 1-3 Mini Review

The Challenge of Specific Cathepsin S Activity Detection in Experimental Settings

Alex Steimle and Julia-Stefanie Frick*

Institute of Medical Microbiology and Hygiene, University of Tuebingen, Tübingen, Germany

In recent years, a growing interest in pathophysiological processes that are associated with the endosomal and lysosomal protease cathepsin S (CTSS) results in an increasing number of various published methods for CTSS activity detection. CTSS has been reported to be involved in the pathology of autoimmune diseases like multiple sclerosis as well as in tumor growth and Alzheimer’s disease. These implications make this enzyme a first class drug target. In order to fully understand the involvement of CTSS in the formation of pathological processes, gene and protein expression analysis is not sufficient. Rather, one should focus on the regulation of its enzymatic activity. Different approaches for CTSS activity detection are available and described. However, some of these approaches are not suitable for a standard laboratory without special equipment or technical expertise or provide other limitations. We have recently published an easy-to-perform protocol for reliable, quantifiable and reproducible CTSS activity detection. In this review we want to discuss our application and compare it with other published methods and protocols. This might help researchers who are interested in CTSS research to decide which application fits best to their technical or personal facilities.

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Vol 1-3 Mini Review

MCPIP mediates preconditioning protection against ischemia

Jianli Niu and Pappachan E. Kolattukudy*

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA

Inflammatory response represents one of the first immune processes following injury. However, evidence indicates that inflammatory response can also induce cellular protection associated with preconditioning, a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. The elucidation of mechanisms that allow inflammatory response to confer cellular protection is critical to developing new therapeutic strategies against acute ischemic insults. In the present review, we will give a short overview on a novel zinc-finger protein, MCPIP (also known as Zc3h12a or Regnase-1), which may function as a master integrator of endogenous cellular protection exerted by preconditioning.

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Vol 1-3 Mini Review

Medical uses of Sodium thiosulfate

Patrick L. McGeer* Edith G. McGeer and Moonhee Lee

Kinsmen Laboratory of Neurological Research, University of British Columbia, VancouverBC V6T 1Z3, Canada

Sodium thiosulfate (STS) is an industrial chemical which also has a long medical history. It was originally used as an intravenous medication for metal poisoning. It has since been approved for the treatment of certain rare medical conditions. These include cyanide poisoning, calciphylaxis, and cisplatin toxicity. In vitro assays have demonstrated that it is an anti-inflammatory and neuroprotective agent. It therefore has potential for treating neurodegenerative diseases such as Alzheimer disease and Parkinson disease. NaSH has similar properties and is somewhat more powerful than STS in these in vitro assays. However STS has already been approved as an orally available treatment. STS may therefore be a readily available candidate for treating neurodegenerative disorders such as Alzheimer disease and Parkinson disease.

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Vol 1-3 Mini Review

Membrane Remodelling Activity of ?-Synuclein

Silvia Campioni1,2, Roland Riek1*

1Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Vladimir-Prelog-Veg 2, 8093 Zurich, Switzerland
2Laboratory of Food and Soft Materials, Department of Health Sciences and Technologies, Swiss Federal Institute of Technology Zurich, Schmelzbergstrasse 9, 8092 Zurich, Switzerland

Despite extensive research, a detailed description of the physiological function of α-Synuclein (α-Syn), the human neuronal protein involved in the pathogenesis of Parkinson’s Disease, is still lacking, most likely due to its highly dynamic conformation and behaviour. Recently, it has become increasingly evident that the interaction of α-Syn with membranes plays an important role in its function and misfunction. Strikingly, despite not having a membrane scaffolding domain, α-Syn can extensively reshape membrane bilayers. Moreover, stable and soluble nanometer-sized particles, whose morphology is ranging from tubules to discoids, can be obtained in vitro with different protocols and from different lipids. The focus of this review article is on the description of the membrane remodelling activity of α-Syn and on its possible physiological role.

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Vol 1-3 Mini Review

Role of the prefrontal cortex in the neonatal ventral hippocampus lesion, an animal model of schizophrenia

Gonzalo Flores1 and Julio Morales-Medina2

1Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, Puebla, México
2Centro de Investigación en Reproducción Animal, CINVESTAV- Universidad Autónoma de Tlaxcala, AP 62, CP 90000, Tlaxcala, México

Schizophrenia is a complex mental disorder that starts at early adulthood with a combination of positive and negative symptoms as well as cognitive impairments. It is well known that dendritic spine density and dendritic length of the pyramidal neurons of the prefrontal cortex (PFC) are reduced in the post-mortem tissue of schizophrenia pateints. In addition, the volume of the PFC is reduced in this mental disorder. A possible hypothesis for these morphological changes suggests that the disruption between PFC and hippocampus, at an early age is involved in the pathophysiology of schizophrenia. Furthermore, rats with bilateral lesion of the neonatal ventral hippocampus (nVHL) at an early age is an example of the initial disruption between hippocampus and PFC and also exhibits a reduction in the synaptic connections in the PFC. The present mini-review discusses the neurochemical and morphological changes in the PFC of rats that underwent nVHL, an animal model of schizophrenia.

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Vol 1-3 Mini Review

DNA-PK Deficiency in Alzheimer's Disease

Jyotshna Kanungo*

Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA

Alzheimer’s disease (AD) is characterized by neuronal death with an accumulation of intra-cellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. Reduced DNA repair ability has been reported in AD brains. In neurons, the predominant mechanism to repair double-strand DNA breaks (DSB) is non-homologous end joining (NHEJ) that requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK is a holoenzyme comprising the p460 kD DNA-PK catalytic subunit (DNA-PKcs) and its activator Ku, a heterodimer of p86 (Ku80) and p70 (Ku70) subunits. Upon binding to double-stranded DNA ends, Ku recruits DNA-PKcs to process NHEJ. In AD brains, reduced NHEJ activity as well as DNA-PKcs and Ku protein levels have been shown. Normal aging brains also show a reduction in both DNA-PKcs and Ku levels questioning a direct link between NHEJ ability and AD, and suggesting additional players/events in AD pathogenesis. Deficiency of Ku80, a somatostatin receptor, can disrupt somatostatin signaling thus inducing amyloid beta (Aβ) generation, which in turn can potentiate DNA-PKcs degradation and consequently loss of NHEJ activity, an additional step negatively affecting DSB repair. Trigger of these two different pathways culminating in genome instability may differentiate the outcomes between AD and normal aging.

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