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Synapsins serve as flagships among the presynaptic proteins due to their abundance on synaptic vesicles and contribution to synaptic communication. Several studies have emphasized the importance of this multi-gene family of neuron-specific phosphoproteins in maintaining brain physiology. In the recent times, increasing evidence has established the relevance of alterations in synapsins as a major determinant in many neurological disorders. Here, we give a comprehensive description of the diverse roles of the synapsin family and the underlying molecular mechanisms that contribute to several neurological disorders. These physiologically important roles of synapsins associated with neurological disorders are just beginning to be understood. A detailed understanding of the diversified expression of synapsins may serve to strategize novel therapeutic approaches for these debilitating neurological disorders.

Alzheimer's disease (AD) has characteristic neuropathological abnormalities including regionalized neurodegeneration, neurofibrillary tangles, amyloid beta (Aβ) deposition, activation of pro-apoptotic genes, and oxidative stress. As the brain functions continue to disintegrate, there is a decline in person's cognitive abilities, memory, mood, spontaneity, and socializing behavior. A framework that sequentially interlinks all these phenomenons under one event is lacking. Accumulating evidence has indicated the role of insulin deficiency and insulin resistance as mediators of AD neurodegeneration. Herein, we reviewed the evidence stemming from the development of diabetes agent-induced AD animal model. Striking evidence has attributed loss of insulin receptor-bearing neurons to precede or accompany initial stage of AD. This state seems to progress with AD such that, in the terminal stages, it worsens and becomes global. Oxidative stress, tau hyperphosphorylation, APP-Aβ deposition, and impaired glucose and energy metabolism have all been linked to perturbation in insulin/IGF signaling. We conclude that AD could be referred to as "type 3 diabetes". Moreover, owing to common pathophysiology with diabetes common therapeutic regime could be effective for AD patients.

Audio segmentation is a basis for multimedia content analysis which is the most important and widely used application nowadays. An optimized audio classification and segmentation algorithm is presented in this paper that segments a superimposed audio stream on the basis of its content into four main audio types: pure-speech, music, environment sound, and silence. An algorithm is proposed that preserves important audio content and reduces the misclassification rate without using large amount of training data, which handles noise and is suitable for use for real-time applications. Noise in an audio stream is segmented out as environment sound. A hybrid classification approach is used, bagged support vector machines (SVMs) with artificial neural networks (ANNs). Audio stream is classified, firstly, into speech and nonspeech segment by using bagged support vector machines; nonspeech segment is further classified into music and environment sound by using artificial neural networks and lastly, speech segment is classified into silence and pure-speech segments on the basis of rule-based classifier. Minimum data is used for training classifier; ensemble methods are used for minimizing misclassification rate and approximately 98% accurate segments are obtained. A fast and efficient algorithm is designed that can be used with real-time multimedia applications.

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J. Neurochem. (2012) 121, 954–963. Abstract Alzheimer’s disease (AD) is the most common form of dementia and cognitive impairment usually characterized by widespread neurodegeneration throughout the association cortex, limbic system and hippocampus. Aberrant protein phosphorylation is a defining pathological hallmark of AD and implicated in the dysregulation of major cellular processes through highly dynamic and complex signaling pathways. Here in, we demonstrate 81 proteins, of 600 spots selected, unambiguously identified as phosphorylated, providing a partial phosphoproteome profile of AD substantia nigra and cortex and respective control brain regions. More importantly, abnormal phosphorylation signal intensity of nine physiologically important proteins observed can profoundly affect cell metabolism, signal transduction, cytoskeleton integration, and synaptic function and accounts for biological and morphological alterations. Our studies employed two‐dimensional gel electrophoresis for protein separation, Pro‐Q® Diamond phosphoprotein staining and electrospray ionization quadrupole time of flight tandem MS for protein identification. NetPhosk 1.0 is used for the confirmation of protein modification status as well known/putative phosphoproteins. A further insight into the links among the identified phosphoproteins and functional roles STRING 8.3, KEGG and REACTOME pathway databases were applied. The present quantitative phosphoproteomic analysis can be supportive in establishing a broad database of potential protein targets of abnormal phosphorylation in AD brain.

Recent studies have uncovered evidence suggesting that interference with hippocampal adult neurogenesis contributes to neurodegeneration in Alzheimer's disease (AD). Evidence supporting that AD is a metabolic disease with derangements in brain glucose utilization implies the use of anti-diabetics as an alternate therapeutic strategy. The present study drew comparison between the pro-neurogenic potential of metformin and donepezil in AlCl-induced mouse model of neurodegeneration. Morris water maze task and subsequent immunohistochemical evaluation for NeuN was conducted. Expression of neurogenesis markers and hippocampal proteome analysis was determined by qRT-PCR and SDS-PAGE, respectively, followed by ESI-QTOFF MS/MS identification. The results demonstrated impaired spatial memory and differential expression of eight proteins in the AlCl group as compared to the controls. Interestingly, treatment with metformin normalized the proteome profile and expression levels of neurogenesis markers along with improvement in the spatial memory. Moreover, as compared to donepezil, metformin-treated mice exhibited an enhanced number of post-mitotic NeuN-positive neurons. It is suggested that underlying molecular mechanisms of metformin-mediated adult hippocampal neurogenesis may have implications in treatment of neurodegenerative disorders.

BackgroundComplex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.ResultsMany proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.ConclusionThese findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.