No quiet surrender: molecular guardians in multiple sclerosis brain

The Journal of Clinical Investigation, 2015 · DOI: 10.1172/JCI74255 · Published: April 1, 2015

Simple Explanation

Multiple sclerosis (MS) is characterized by the capacity for patients to spontaneously recover from neurologic deficits attributed to inflammatory attacks on the CNS. The brain in MS responds to immune damage with molecules that protect it from further damage and foster recovery, involving cells both extrinsic and intrinsic to the CNS. This review describes guardian molecules like protective cytokines, neurotrophins, neurotransmitters, antioxidants, myelin sheath lipids, nuclear hormone receptors, amyloid-forming molecules, and inhibitory proteins as platforms for novel restorative therapies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Protective cytokines like IL-10 and IL-27, produced by immune cells migrating into the brain or by resident glia and neurons, attenuate inflammation in MS.
2
Neurotrophins such as BDNF and NGF have antiinflammatory properties and promote neural outgrowth, contributing to the resolution of neuroinflammation in MS lesions.
3
Amyloid-forming molecules, including CRYAB, APP, and prion proteins, found in MS lesions, may contain ongoing inflammation and initiate repair, contrary to their conventional association with pathology in Alzheimer’s disease.

Research Summary

The brain under immunological attack in MS reveals a coordinated molecular response involving various proteins and small molecules that provide protection and foster repair. Reduction of inflammation serves as a necessary prerequisite for effective recovery and regeneration in MS. Guardian molecules and their corresponding physiologic pathways could be exploited to silence inflammation and repair the injured brain and spinal cord in MS.

Practical Implications

Therapeutic Potential of Guardian Molecules

Identifying and delivering protective molecules to the brain structures under attack could lead to novel restorative therapies for MS.

Targeting Multiple Pathways

Therapies that can simultaneously inhibit autoimmunity and promote protection and regeneration may be more effective in treating MS.

Rethinking Amyloid Molecules

Further research into the protective roles of amyloid-forming molecules in neuroinflammatory conditions could lead to new therapeutic directions.

Study Limitations

1
The review focuses primarily on molecular mechanisms and preclinical models, with limited discussion of clinical trials.
2
The complexity of MS pathology suggests that a single 'guardian molecule' may not be sufficient for effective treatment.
3
The review acknowledges the Janus faces of certain molecules, indicating the need for careful consideration of potential adverse effects.

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