# Stepchild or Prodigy? Neuroprotection in Multiple Sclerosis (MS) Research

**Authors:** Andrea Rottlaender, Stefanie Kuerten

PMC · DOI: 10.3390/ijms160714850 · 2015-07-01

## TL;DR

This review highlights the importance of developing neuroprotective therapies for multiple sclerosis, as current treatments focus on the immune system and not on protecting nerve fibers.

## Contribution

The paper emphasizes the need for target-oriented neuroprotective strategies in MS treatment.

## Key findings

- Current MS therapies focus on immune modulation rather than neuroprotection.
- Axonal damage correlates with neurological disability in MS.
- Neuroprotective strategies are essential for treating progressive MS.

## Abstract

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities.

## Linked entities

- **Diseases:** multiple sclerosis (MONDO:0005301), MS (MONDO:0006861)

## Full-text entities

- **Genes:** CNTF (ciliary neurotrophic factor) [NCBI Gene 1270] {aka HCNTF}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, TOB1 (transducer of ERBB2, 1) [NCBI Gene 10140] {aka APRO5, APRO6, PIG49, TOB, TROB, TROB1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, NELFCD (negative elongation factor complex member C/D) [NCBI Gene 51497] {aka HSPC130, NELF-C, NELF-D, TH1, TH1L}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, RTN4 (reticulon 4) [NCBI Gene 57142] {aka ASY, NI220/250, NOGO, NOGOA, NOGOB, NSP}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, GAP43 (growth associated protein 43) [NCBI Gene 2596] {aka B-50, GAP-43, PP46}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, LINGO1 (leucine rich repeat and Ig domain containing 1) [NCBI Gene 84894] {aka LERN1, LRRN6A, MRT64, UNQ201}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, SLC24A3 (solute carrier family 24 member 3) [NCBI Gene 57419] {aka NCKX3}, CASP2 (caspase 2) [NCBI Gene 835] {aka CASP-2, ICH1, MRT80, NEDD-2, NEDD2, PPP1R57}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, SCN8A (sodium voltage-gated channel alpha subunit 8) [NCBI Gene 6334] {aka BFIS5, CERIII, CIAT, DEE13, EIEE13, MED}, RXRG (retinoid X receptor gamma) [NCBI Gene 6258] {aka NR2B3, RXR-gamma, RXRC, RXRgamma}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, Large1 (LARGE xylosyl- and glucuronyltransferase 1) [NCBI Gene 16795] {aka BPFD#36, Gyltl1a, Large, Mbp-1, Mbp1, enr}
- **Diseases:** Brain atrophy (MESH:C566985), axonal damage (MESH:D001480), nervous system (MESH:D009422), inflammation (MESH:D007249), EAE lesion (MESH:D009059), autoimmune disorder of the central nervous system (MESH:D020274), neurological disability (MESH:D009069), spinal cord lesions (MESH:D013118), mitochondrial collapse (MESH:D001261), CNS damage (MESH:D002493), brain lesions (MESH:D001927), axonal pathology (MESH:D005598), hypertrophy (MESH:D006984), autoimmune (MESH:D001327), disease of the (MESH:D004194), Wallerian degeneration (MESH:D014855), Neurodegeneration (MESH:D019636), Mitochondrial damage (MESH:D028361), transection (MESH:D020221), motor and sensory deficits (MESH:D001289), axonal atrophy (MESH:D001284), axonal swelling (MESH:D004487), mitochondria (MESH:C564971), experimental autoimmune encephalomyelitis (MESH:D004681), cognitive and psychological impairment (MESH:D003072), neurological diseases (MESH:D020271), Nerve fiber injury (MESH:D000080902), deficit (MESH:D009461), neuroinflammatory (MESH:D000090862), cytotoxic (MESH:D064420), MS (MESH:D009103), axonal death (MESH:D003643), axonal (MESH:D012183), Nerve Fiber (MESH:D000071075), Neuronal Damage (MESH:D009410), axonal and myelin loss (MESH:D003711)
- **Chemicals:** progesterone (MESH:D011374), sodium (MESH:D012964), N-acetylaspartate (MESH:C000179), Free radicals (MESH:D005609), lipid (MESH:D008055), lamotrigine (MESH:D000077213), NO (MESH:D009569), calcium (MESH:D002118), water (MESH:D014867), superoxides (MESH:D013481), reactive oxygen and nitrogen species (-), Minocycline (MESH:D008911), GA (MESH:D000068717), phospholipid (MESH:D010743), Glutamate (MESH:D018698), tetracycline (MESH:D013752),  (MESH:D018696)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4519875/full.md

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Source: https://tomesphere.com/paper/PMC4519875