Title

Amyotrophic Lateral Sclerosis: Is The Spinal Fluid Pathway Involved In Seeding And Spread?

Department

neurobiology

Document Type

Article

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder manifested primarily by loss of upper and lower motor neurons. Current explanations for disease progression invoke regional spread attributed to the transfer of pathogenic factors among physically contiguous neurons. However, this explanation incompletely explains certain clinical and in vitro data. Considering this, we propose that the cerebrospinal fluid (CSF) pathway is likely to be a key vector for seeding local and distal disease. Subsequent disease progression would be expected to occur independently via either axonal or CSF transmission.If one accepts the hypothesis that the CSF pathway is involved in ALS progression, it follows that the choroid plexus (CP) might well be a driver of the disease process. In support of this, we briefly review the anatomical and physiological features of the CSF pathway and the choroid plexus responsible for secreting CSF. In addition, we draw attention to the interface of the CP and CSF with the immune system. We then summarize both clinical and cell culture research that supports a key role of the CSF in the establishment and inter-neuronal spread of ALS, and which suggest directions for translational research.

Publication Date

11-1-2015

Publication Title

Medical Hypotheses

ISSN

03069877

Volume

85

Issue

5

First Page

576

Last Page

583

Digital Object Identifier (DOI)

10.1016/j.mehy.2015.07.014

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