CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury

Abstract

Neurodegeneration in the adult mammalian central nervous system (CNS) is fundamentally accelerated by its intrinsic neuronal mechanisms, including its poor regenerative capacity and potent extrinsic inhibitory factors. Thus, the treatment of neurodegenerative diseases faces many obstacles. The degenerative processes, consisting of axonal/dendritic structural disruption, abnormal axonal transport, release of extracellular factors, and inflammation, are often controlled by the cytoskeleton. From this perspective, regulators of the cytoskeleton could potentially be a therapeutic target for neurodegenerative diseases and CNS injury. Collapsin response mediator proteins (CRMPs) are known to regulate the assembly of cytoskeletal proteins in neurons, as well as control axonal growth and neural circuit formation. Recent studies have provided some novel insights into the roles of CRMPs in several inhibitory signaling pathways of neurodegeneration, in addition to its functions in neurological disorders and CNS repair. Here, we summarize the roles of CRMPs in axon regeneration and its emerging functions in non-neuronal cells, especially in inflammatory responses. We also discuss the direct and indirect targeting of CRMPs as a novel therapeutic strategy for neurological diseases.

Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein‐2 drive reinstatement of alcohol reward seeking

“…; Nagai et al . ). We previously reported that excessive alcohol consumption promotes the mTORC1‐dependent translation of CRMP2 in the NAc, resulting in increased microtubule assembly (Liu et al .…”

The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells

“…CRMP1, a member of the the Collapsin Response Mediator Proteins (CRMPs) family, regulates many aspects of cytoskeletal remodeling and arborization of neurites and dendrites in neuronal cells (Yamashita and Goshima, 2012 ; Quach et al, 2015 ; Nagai et al, 2017 ). Phosphorylation status of CRMP1 affects the signaling pathways mediated by Semaphorin 3A (SEMA3A) and reelin (Yamashita et al, 2006 ); notably, the latter was an up-regulated gene in our wtPPT1 overexpressing cells (see Figure 7 ).…”

Proteomic Studies Reveal Disrupted in Schizophrenia 1 as a Key Regulator Unifying Neurodevelopment and Synaptic Function

“…The 5 top canonical pathways involved in our analysis are represented in Table 2. It is interesting that CRMP (collapsin response mediator protein) family was highlighted in the analysis as part of the Semaphorin signaling in neurons, since this signaling cascade is known to play an important role in neuronal differentiation and axonal growth [29,30]. Previous studies also concluded that the overexpression of the truncated isoform of DISC1 leads to dysregulation of Semaphorin signaling [20].…”