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Why does multiple sclerosis only affect human primates?
1University of Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands hart@bprc.nl.
Background:
Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as insights might be gained into the elusive event(s) that trigger(s) MS. A well-established difference between the human primate (Homo sapiens) and non-human primates is that humans are unable to synthesize the sialic acid N-glycolylneuraminic acid (Neu5Gc).
Viewpoint:
We propose the concept that long-term ingestion by human primates of the foreign Neu5Gc, via red meat consumption, is an ignored environmental risk factor for MS. Conceptually, incorporation of dietary Neu5Gc into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit, creates targets for binding of de novo synthesized heterophilic anti-NeuGc antibodies. Binding of the antibodies can cause BBB leakage and destabilization of the axon-myelin coupling. The ensuing cytodegeneration and release of self-antigens could be a start of the characteristic pathological features of MS.
Insights
Humans cannot produce N-glycolylneuraminic acid (Neu5Gc), unlike other primates. Dietary Neu5Gc from red meat may trigger multiple sclerosis (MS) by forming targets in the central nervous system for antibody attack.
Area of Science:
- Neuroimmunology
- Human Biology
- Dietary Medicine
Background:
- Multiple sclerosis (MS) is a human-exclusive disease, while non-human primates are resistant, despite susceptibility to experimental autoimmune encephalomyelitis (EAE).
- Humans uniquely cannot synthesize N-glycolylneuraminic acid (Neu5Gc), a sialic acid absent in non-human primates.
Purpose of the Study:
- To investigate the discrepancy in MS susceptibility between humans and non-human primates.
- To explore potential environmental triggers for MS, focusing on dietary factors.
Main Methods:
- Comparative analysis of human and non-human primate biology regarding sialic acid synthesis.
- Hypothesizing the role of dietary Neu5Gc in MS pathogenesis.
Main Results:
- Humans' inability to synthesize Neu5Gc distinguishes them from non-human primates.
- Dietary Neu5Gc, obtained from red meat, is proposed as a novel environmental risk factor for MS.
Conclusions:
- Incorporation of dietary Neu5Gc into the central nervous system may create targets for anti-Neu5Gc antibodies.
- Antibody binding to Neu5Gc could lead to blood-brain barrier dysfunction and myelin damage, initiating MS pathology.
