Clinical proteomics of enervated neurons

摘要

The dynamic field of neurosciences entails ever increasing search for molecular mechanisms of disease states, especially in the domain of neurodegenerative disorders. The previous century heralded the techniques in proteomics when indexing of the human proteomes relating to various disease conditions became important. Early stage research in certain diseases or pathological conditions requires a more holistic approach of first discovering the proteins of interest for the condition. Despite its limitations, proteomics is one of the most powerful techniques available to us today to dissect the molecular scenario in a particular disease situation. In this review we will discuss about the current clinical research in neurodegenerative disorders that employ proteomics techniques. We will specifically focus on our understanding of Alzheimer's disease, traumatic spinal cord injury and neuromyelitis optica. Discussions will include ongoing worldwide research in these areas, research in India and specifically our laboratory in these domains of neurodegenerative conditions. The most polarized cells of the human body, neurons, are a specialized type with respect to their functional properties. Development and function of neurons are closely linked to the bidirectional transport of molecules from the synaptic end to the cell body. This very synaptic signal, which when disrupted, causes the dysfunction of neuronal activities. Disruption in axonal transport is the cause of several neurodegenerative disorders [1, 2]. In the realm of peripheral neuron injury, retrograde transport of molecules from the site of injury to the cell body of a peripheral neuron primes the latter to regenerate [3, 4]. This phenomenon is absent in the central nervous system (CNS), with the consequence of regeneration after CNS injury being elusive even with years of research. Partly because of the large distance separating the axon end from the cell body, many molecular events after a trauma or a neuronal disease occur without any transcriptional manifestations [5]. Local proteolysis, protein synthesis and post translational modifications are the key to understanding axonal events after an assault or a disorder of the neuron [5]. Proteomics approaches have therefore come to the limelight in recent times. In this review, we will discuss the contributions of our group from this perspective and also the prospective ideas in three neurological degenerative situations, namely Alzheimer's disease (AD), traumatic spinal cord injury (SCI) and neuromyelitis optica (NMO) and explore the advances in understanding these pathological processes using proteomics approaches.