Play in advance against neurodegeneration: exploring enteric glial cells in gut-brain axis during neurodegenerative diseases

ABSTRACT

Introduction: New investigations have shown that ‘activated’ enteric glial cells (EGCs), astrocyte-like cells of the enteric nervous system (ENS), represent a possible extra-CNS trigger point of the neurodegenerative processes in impaired intestinal permeability conditions. The early modulation of enteric glia-mediated neuroinflammation might optimize neuroprotective treatments outcomes currently used in neurodegenerative diseases.

Areas covered: We discussed recent clinical and preclinical data existing on the Pubmed database, concerning the glial role in neurodegeneration. We focused on the gut as possible “entrance door” for endoluminal neurotoxic agents that induce neurological impairments during leaky gut conditions. Moreover, we reviewed the paradigmatic studies linking the leaky gut-induced priming of EGCs to the induction of late neurodegenerative processes in Parkinson’s disease and other neurodegenerative disorders.

Expert opinion: The previous appearance of neuropathological markers in the ENS emphasizes the extra-CNS origin of neurodegenerative disorders, by directing their therapies toward peripheral management of neurodegeneration. In light of the EGCs changes resulting from a switch-on of activated phenotype in leaky gut syndrome, EGCs sampling could be predictive for neuropathological conditions detection, anticipating their symptomatic manifestation in the CNS.

KEYWORDS:

• Neurodegenerative diseases
• glial-sustained neuroinflammation
• leaky gut
• enteric nervous system
• enteric glial cells
• gut-brain axis

Article highlights

• Neurodegenerative diseases: a brief overview and the main limitations of current therapies

• From ‘neuron-centric’ to ‘glial-centric’ view of neurodegeneration

• The gut-brain axis concept in neurodegeneration: exploring the enteric nervous system

• Leaky gut condition: a key event in the extra-CNS origin of neurodegenerative diseases

• Enteric glial cell: the missing link at the basis of the gut-brain axis

• Emerging evidence of EGCs role in the development of the neurodegenerative disorders

• The study of EGCs for early diagnosis of neurodegenerative disorders and novel neuroprotective drugs development acting at extra-CNS sides?

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.