nAChR, agrin, rapsyn and ME

Nicotinic acatylcholine receptors (nAChRs) are suspected to be involved in the ME pathomechanism (1).

ME patients have dysregulated lipid metabolism (2). This could have an impact on lipid rafts?

Lipid rafts serve as signaling platforms for nAChRs clustering. The clustering is induced by the heparan sulphate proteoglyan, agrin. The nAChRs are anchored into the lipid rafts by rapsyn (3).

A proteomic study on cerebrospinal fluid from ME patients has shown an upregulation of the arin precursor and of the heparan sulfate proteoglyan core protein precursor (4).

The gene RAPSN (protein: rapsyn) has been found epigenetic changed (hypermethylated) in ME (5).

References:

1. Griffith University. https://www.griffith.edu.au/health/national-centre-neuroimmunology-emerging-diseases
2. Naviaux et al: Metabolic features of CFS. www.pnas.org/cgi/doi/10.1073/pnas.1607571113
3. Allen et al: Lipid raft microdomains and neurotransmitter signalling. Nature Reviews, feb 2007, vol 8.
4. Schutzer et al: Distinct Cerebrospinal Fluid Proteomes Differentiate Post- Treatment Lyme Disease from Chronic Fatigue Syndrome. PLOS One February 2011, volume 6, Issue 
5. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e104757

Pyruvate and ME/POTS

Fluge, Mella et al. have shown that ME is associated with defective oxidative metabolism - most likely involving impaired pyruvate dehydrogenase function (1).

Expression of the protein mitochondrial pyruvate carrier 2 (MCC2) has been found downregulated in ME (2)

The gene similar to pyruvate kinase-isozymes M1/M2 (PKM2) has been found epigenetic changed (hypermethylated) in ME (3).

Immunoreactive proteins against IgGs from POTS patients (4, 5):

• ODPB, pyruvate dehydrogenase E1 component subunit beta.
• KPYM, pyruvate kinase isoenzyme M1.
• PDHX, pyruvate dehydrogenase protein X component.
• PKM2, pyruvate kinase isozymes M1/M2

References:

1.  Fluge et al: Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy / chronic fatigue syndrome. JCI Insight. 2016; 1(21):e89376. Doi 10.1172/jci.insight.89276
2. Ciregia et al.
   Translational Psychiatry (2016), 6, e904
   doi:10.1038/tp.2016.184
3. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e104757
4. Wang et al: Autoimmunoreactive IgGs from patients with POTS. Prot. Clin. Appl. 2012, 6, 1-11.
5. Wang et al: Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with POTS. doi: 10.1016/j.trsl.2013.03.002