Role of Dynein and Dynactin (DCTN-1) in Neurodegenerative Diseases

Abstract

The pathophysiology and concept of degeneration in central nervous system is very complex and overwhelming at times. There is a complex mechanism which exists among different molecules in the cytoplasm of cell bodies of neurons, antegrade and retrograde axonal transport of cargoes and accumulation of certain substances and proteins which can influence the excitatory neurotransmitter like glutamate initiating the process of neurodegeneration. Neurons have extensive processes and communication between those processes and the cell body is crucial to neuronal function, viability and survival over time with progression of age. Researchers believe neurons are uniquely dependent on microtubule-based cargo transport. There is enough evidence to support that deficits in retrograde axonal transport contribute to pathogenesis in multiple neurodegenerative diseases. Cytoplasmic dynein and its regulation by Dynactin (DCTN1) is the major molecular motor cargo involved in autophagy, mitosis and neuronal cell survival. Mutation in dynactin gene located in 2p13.1,is indeed studied very extensively and is considered to be involved directly or indirectly to various conditions like Perry syndrome, familial and sporadic Amyotrophic lateral sclerosis, Hereditary spastic paraplegia, Spinocerebellar Ataxia (SCA-5), Huntingtons disease, Alzheimers disease, Charcot marie tooth disease, Hereditary motor neuropathy 7B, prion disease, parkinsons disease, malformation of cortical development, polymicrogyria to name a few with exception of Multiple Sclerosis (MS).

Spatiotemporal patterns of gene expression around implanted silicon electrode arrays

“…In addition to neuronal cytoskeletal perturbations, we observed significant downregulation of several synapse-associated genes in interfacial tissue, particularly during the first week post-implantation (including CaMKIIa, Syn1, Stxbp1, Bsn, Arc, Gabbr1/2, Cacna1i and Cacng3) (figure 3) [71]. Several of these genes are associated with regulating vesicular release.…”

“…EMC degradation, apoptosis, clathautophagy, and glia induced cell death [67] Ctsl Cathepsin L Cysteine protease. EMC degradation, apoptosis, autophagy, and glia induced cell death [68] Cx3cr1 CX3C chemokine receptor 1 Cytokine signaling [31,69] Cxcl1 C-X-C motif chemokine ligand 1 Cytokine signaling [31,70] Cxcl2 C-X-C motif chemokine ligand 2 Cytokine signaling, inflammation, and BBB transmigration [71] Cyfip2 Cytoplasmic FMR1 interacting protein 2 Regulations of mRNA translation at the synapse. Synapse maintenance [72,73]…”