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Protein Post-Translational Modifications in the Nervous System: from Development to Disease and Ageing
Post-translational modifications (PTMs) increase the functional diversity of the proteome by reversibly or irreversibly modifying proteins during or after their synthesis. Thereby, they contribute to the structural and functional variety of proteins, conveying a complexity to the proteome that is significantly higher than the coding capacity of the genome. Moreover, providing another level of epigenetic regulation, PTMs of histone proteins in particular contribute to the modulation of gene accessibility and specific cell expression profiles. PTMs include enzymatically controlled modifications such as phosphorylation, glycosylation, acetylation, methylation, ubiquitination, or proteolysis as ...
The Proteasome in Neurodegeneration
In the last 50 years a wealth of information has allowed us to understand the contribution of various regulatory factors that alter mRNA and protein s- thesis to a variety of physiological and pathological conditions. However, such regulation is only one of many factors that contribute to the levels of a given p- tein. One major factor that has been relatively obscure until recently has been the contribution of protein degradation to the regulation of the steady state level of protein expression and protein function. This rapidly evolving field has made a significant mark on the scientific community, as highlighted by the Award of the Nobel Prize in Chemistry for 2004 to Aaron Ciechanover, A...
ATP-gated P2X receptors in health and disease
Extracellular ATP is currently recognized as one of the most widely distributed neurotransmitters and neuromodulators in the peripheral and central nervous system. ATP-gated P2X receptors are expressed by neurons, glial and many other non-neuronal cells and represent an attractive target for therapeutic interventions. Diverse molecular and cellular mechanisms have been identified for P2X receptor functioning, including the ability to enlarge the size of the ion pore associated with the release of several key immune molecules. A major recent breakthrough was the determination of the X-ray crystal structures of zebrafish P2X4 receptor in ATP-bound and ATP-free states. The P2X receptor research...
Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP)
Phosphatases, such as TNAP are fundamental in regulating the roles of cellular, and consequently numerous body functions. TNAP is a ubiquitous enzyme with a wide spectrum of substrates and specificity. Regulation at the cellular level and the lack of TNAP activity is a lethal condition. Recent findings of a highly specific regional, laminar and subcellular localization of TNAP in the cerebral cortex indicates that in addition to its metabolic and skeletal functions, TNAP also plays a role in regulating cerebral functions, most probably cognition. In fact, TNAP disturbance could result in complex diseases such as epilepsy, developmental retardation and Alzheimer's disease. Available data suggest that, regarding brain functions, TNAP is a potentially important target of clinical research. This book aims to provide an overview of our current understanding of the functions of TNAP in the brain and on other tissues and organs.
