Role of Platelets in Neurodegenerative Diseases: A Universal Pathophysiology.

All India Institute of Medical Sciences, Neurology , Ansari Nagar, New Delhi , 110029 India.
The International journal of neuroscience (Impact Factor: 1.52). 01/2013; 123(5). DOI: 10.3109/00207454.2012.751534
Source: PubMed


Abstract Platelets play an important role in a variety of disorders viz; cardiovascular, psychosomatic, psychiatric, thrombosis, HIV/AIDS in addition to various neurodegenerative diseases (NDD). Recent evidence indicates that platelet react to diverse stressors thereby offering an interesting vantage point for understanding their potential role in contemporary medical research. This review addresses the possible role of platelets as a systemic probe in various NDD's such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Huntington's Disease (HD), Alzheimer's Disease (AD), Multiple Sclerosis (MS) etc. The current review based on published literature, describes a probable link between platelets and pathophysiology of various NDD's. It also discusses how platelets epitomize ultra structural, morphological, biochemical and molecular changes, highlighting their emerging role as systemic tools in different NDD's.

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    • "Recent evidence indicates the interrelation between changes in glutamate transport and metabolism in the brain and platelets (Aliprandi et al., 2005; do Nascimento et al., 2006; Rainesalo et al., 2003; Rolf et al., 1993; Yao et al., 2006; Zoia et al., 2004), and so the possible role of platelets as a diagnostic marker in various neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, multiple sclerosis, etc. (Behari and Shrivastava, 2013). Demonstrating the similarity with nerve terminals in: (1) glutamate uptake by glutamate transporters and mechanisms of its regulation; (2) accumulation of cytosolic glutamate into acidic compartments, dense secretory granules, by vesicular glutamate transporters and exocytotic release of glutamate during activation; (3) existence of NMDA, AMPA and mGlu 3, 4 receptors in the plasma membrane; platelets (in contrast to nerve terminals) cannot release glutamate in non-exocytotic manner (Fig. 9). "
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    ABSTRACT: Platelets express neuronal and glial glutamate transporters EAAT 1-3 in the plasma membrane and vesicular glutamate transporters VGLUT 1,2 in the membrane of secretory granules. This study is focused on the assessment of non-exocytotic glutamate release, that is, the unstimulated release, heteroexchange and glutamate transporter reversal in platelets. Using the glutamate dehydrogenase assay, the absence of unstimulated release of endogenous glutamate from platelets was demonstrated, even after inhibition of glutamate transporters and cytoplasmic enzyme glutamine synthetase by dl-threo-β-benzyloxyaspartate and methionine sulfoximine, respectively. Depolarization of the plasma membrane by exposure to elevated [K+] did not induce the release of glutamate from platelets that was shown using the glutamate dehydrogenase assay and radiolabeled l-[14C]glutamate. Glutamate efflux by means of heteroexchange with transportable inhibitor of glutamate transporters dl-threo-β-hydroxyaspartate (dl-THA) was not observed. Furthermore, the protonophore cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) and inhibitor of V-type H+-ATPase bafilomycin A1 also failed to stimulate the release of glutamate from platelets. However, exocytotic release of glutamate from secretory granules in response to thrombin stimulation was not prevented by elevated [K+], dl-THA, FCCP and bafilomycin A1.
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    ABSTRACT: Unlabelled: Accurate biomarker quantification requires carefully chosen normalisation procedures. When single proteins are used as loading controls (LCs), it is crucial that their expressional stability must be known. Platelets are an important biomarker source, especially for neurological diseases. We performed a systematical analysis of the platelet proteome to identify proteins suitable as LCs, using the 2-D DIGE system. We first screened a healthy population (n=137), aged between 18 and 104years, to find proteins with small coefficients of total variation (CVtot), herein termed low biological variation proteins (LBVP). Thereafter, expressional stability was verified in 101 patients suffering from Alzheimer's- (AD), Parkinson's- disease, vascular dementia or schizophrenia. Interestingly, traditional LCs such as tubulin beta-1 and GAPDH, were not found amongst LBVP. The least variable protein, calculated over all 238 individuals, was 14-3-3 gamma, with a CVtot of 9.3%, showing no gender, age or disease dependency. The normalisation capability of 14-3-3 gamma was superior to traditional LC in quantifying Western blot signals of the platelet AD-biomarker Monoamine Oxidase B of patient versus controls. Similar results were obtained with HepG2 cells, treated in vitro with DNA-methyltransferase inhibitor 5-aza-2'deoxicytidine. Finally, we provide a list of alternative normalisation candidates for accurate biomarker quantification. Biological significance: This paper suggests a considerable list of platelet proteins with a lower biological variation than well known "housekeeping" proteins like GAPDH and tubulin. Spot abundances of found proteins are middle ranged and unaffected by gender, age and certain diseases. Hence, listed proteins might be valuable normalisation candidates used additionally or alternatively. Platelet's least variable protein 14-3-3 gamma is validated as normalisation protein in platelet biomarker quantification. Furthermore 14-3-3 gamma is demonstrated to be also stable expressed by in HepG2, cells others than platelets, when treated by DNA methylation inhibitor.
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