Neuroscience

The Blood-brain barrier (BBB) is composed of a network of vessels that form a structural and chemical barrier between the brain and systemic circulation. Vessels of the BBB are composed of specialized endothelial cells that lack fenestration (pores that allow rapid exchange of molecules between vessels and tissue), have few pinocytic vesicles to minimize uptake of extracellular substances, and have extensive tight junctions that severely restrict cell permeability. Limited permeability restricts movement of substances from the systemic circulation to the brain which buffers the brain from rapid changes in ionic or metabolic conditions. Limited BBB permeability also protects the brain from exposure to molecules that are harmless to peripheral organs but toxic to neurons in the brain. BBB permeability is influenced by neurons, the extracellular matrix, and non-neuronal cells including astrocytes, pericytes, and vascular endothelial cells. These cells, along with the extracellular matrix, function as a neurovascular unit to regulate BBB permeability and maintain the integrity and function of the central nervous system.

Neural Stem Cells (NSCs) are the most primordial and uncommitted cells of the nervous system, and are believed to give rise to the vast array of more specialized cells of the CNS and peripheral nervous system (PNS). To be considered a “neural stem cell,” in contrast to a “progenitor” cell (i.e., cells that have already become lineage committed to give rise to only one category of neural component, e.g., glial cells versus neurons), that cell must be capable of (1) generating all neural lineages (neurons, astrocytes, and oligodendrocytes) throughout the nervous system, (2) having some capacity for self-renewal, and (3) being able to give rise to cell types in addition to themselves through asymmetric cell division

Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Common neurodegenerative diseases include Alzheimer’s disease and Parkinson’s disease.

Inflammatory processes contribute to neurological disorders, and many therapeutic breakthroughs in neurological disease have been immune-targeted.Neuroinflammation refers to the inflammation of the nervous tissue, and is an immune response often initiated against a variety of harmful stimuli such as pathogens or trauma. Neuroinflammation is a complex biological response involving many signaling proteins, receptors, and cell types. Neuroinflammation stems from a combination of responses from resident glial cells in the central nervous system (CNS), which include microglia, oligodendrocytes, astrocytes, and non-glial resident myeloid cells (macrophages and dendritic cells) and peripheral leukocytes.

A neurotransmitter (NT) is a small molecule released at the presynaptic axonal membrane of one neuron into the synaptic cleft to bind with the receptors present in the postsynaptic membrane of another neuron (or muscle fiber), which results in either excitation or inhibition of the passage of signals across the synapse.

Neurotransmitter receptors are expressed on the surface of post-synaptic cells to bind ligand-specific neurotransmitters and hormones. They are also expressed on presynaptic cells to provide feedback mechanisms and attenuate excessive neurotransmitter release. The majority of neurotransmitter receptors are integral membrane proteins with seven transmembrane domains, commonly coupled to G-proteins. Binding of a ligand to its specific neurotransmitter receptor may result in the activation of a myriad of cell signal transduction pathways and modulation of ion channel homeostasis.

Neurotrophic factors are important regulators of the development and maintenance of vertebrate nervous system. During the development of the nervous system, neuronal populations undergo a process of naturally occurring cell death at a time when their axons are innervating target areas. This mechanism ensures a balance between the size of an innervating population and the size of its target territory. Nerve growth factor (NGF) was the first neurotrophic factor to be discovered. More recent work has shown that other molecules are secreted by target organs that regulate neuronal survival and differentiation. This chapter focuses on neurotrophins with brief descriptions of the actions of these other molecules.

Synaptic Proteins are a family of neuron-specific phosphoric proteins associated with synaptic vesicles. They are present on the surface of almost all synaptic particles and bind to the cytoskeleton. They can be phosphorylated by calmodulin and camp-dependent protein kinases.Human synaptic protein A1 is composed of 705 amino acid residues, and B1 is the product of variable splicing. Presynaptic receptor is a structure between neurons, collectively known as the synapse, composed of the presynaptic membrane, synaptic gap and postsynaptic membrane. The presynaptic receptor refers to a receptor in the presynaptic membrane, which is essentially a protein