Neuromuscular junction in cell necrosis and apoptosis

ABSTRACT

The neuromuscular junction (NMJ) is a unique, specialized chemical synapse that plays a crucial role in transmitting and amplifying information from spinal motor neurons to skeletal muscles. NMJ complexity ensures closely intertwined interactions between numerous synaptic vesicles, signaling molecules, ion channels, motor neurons, glia, and muscle fibers, making it difficult to dissect the underlying mechanisms and factors affecting neuro-degeneration and muscle loss. Muscle fiber or motor neuron cell death followed by rapid axonal degeneration due to injury or disease has a debilitating effect on movement and behavior, which adversely affects the quality of life. It thus becomes imperative to study the synapse and intercellular signaling processes that regulate plasticity at the NMJ and elucidate mechanisms and pathways at the cellular level. The neuromuscular junction (NMJ) is the site of communication between motor nerve axons and skeletal muscle fibres, it is composed of four specialized cell types; Motor neurons, schwann cells, muscle fibre and the recently discovered kranocyte, the functions of the NMJ is to transmit signals from the motor neuron to the skeletal muscle fibre quickly and readily to ensure precise control of skeletal muscle contraction and therefore voluntary movement. The ability of the transmission is aided by specialized architecture (multiple active zone junctional folds) that promotes high level of transmitter released, large and reliable postsynaptic responses to transmitter binding and rapid termination of signaling event. The site where the terminus of a motor neuron (axon) meets with skeletal muscle firbre is quite complex. The motor neuron is a myelinated one, each of the branch produced by the nerve fibre is in close proximity with the muscle fibre membrane and each of the branches of the motor neuron invaginated in the muscle fibre but however, lie totally outside the skeletal muscle fibre membrane (sarcolemma).The motor nerve (axon) contain many sac-like structure known as mitochondria, suspended also in the intracellular fluid of the axon terminus are many tiny dots/sacs referred to as vesicles  in which are stored the synthesized acetylcholine (ACh) molecules. These dots are better known as synaptic vesicles several hundred are usually within each branch of the nerve terminus. The vesicles contains membrane protein called synapto-brevin which when fuses with the axon membrane protein synthaxin brings about exocytotic release of its (ACh) contents into the synaptic cleft and the binding of the released neurotransmitter to its receptors brings about muscle contraction.