Table 3.
Relationships between neurodegenerative disorders and TMAO in different experimental conditions.
| Experimental conditions | Remarks | References |
|---|---|---|
| Human | Detection of TMAO in cerebrospinal fluid. It seems that TMAO levels are not related to neurological disorders (although it was not the objective of the study). | Del Rio D et al., 2017 |
| Synthesized and purified Aβ peptides | TMAO is able to stabilize and modify the aggregation of the peptide Aβ, favouring and accelerating the transformation of the random string of the Aβ peptide to its β-conformation and stabilizing the resulting protofibrils, that can originate fibers that tend to aggregate and form tangled plates. | Yang DS Et al., 1999 |
| Wild and mutant tau proteins | TMAO is able to promote and enhance the assembly of microtubules in mutant and hyperphosphorylated tau protein, reaching in the majority of cases a greater protein efficiency ratio than in wild-type tau. | Smith MJ Et al., 2000 |
| Purified human recombinant tau | TMAO does not act by dephosphorylating tau protein; it facilitates the binding between tau protein and tubulin by reducing the critical concentration of tubulin necessary for assembly. | Tseng HC et al., 1999 |
| Human | TMAO has been suggested to cause blood brain barrier disruption by reducing the expression of tight junction proteins like claudin-5 and tight junction protein-1 (ZO-1). | Subramaniam S et al., 2018 |
| Purified tau proteins | TMAO can act as a natural osmolyte and stimulates tau-induced tubulin assembly | Tseng HC and Graves DJ, 1998 |
| Scrapie-infected mouse neuroblastoma cells | TMAO inhibits the conversion of the scrapie prion protein (PrPC) into its pathogenic isoform (PrPSc), which is associated with transmissible spongiform encephalopathies. | Tatzelt J et al., 1996 |
| BHK-21 and Neuro2a cells transfected with N-terminal truncated ataxin-3 with an expanded polyglutamine stretch | TMAO has been shown to reduce aggregate formation, cell death and cytotoxicity induced by truncated expanded ataxin-3, which is involved in Machado-Joseph disease/spinocerebellar ataxia-3. | Yoshida H et al., 2002 |
| Mice | A lipophilic derivative of TMAO showed an improvement in neurological functions in mice, preventing endothelial reticulum-stress induced apoptosis of NSC-34 motor neuron-like cells and primary mouse astrocytes. | Getter T et al., 2015 |
| α-synuclein peptides | TMAO suppresses the formation of extended conformations and can act as a protecting osmolyte leading to compact and folded forms of α-synuclein. This effect could probably prevent the alpha-synuclein aggregation and formation of insoluble fibrils that cause Parkinson disease. | Jamal S et al., 2017 |
| Purified recombinantα –synuclein | When the concentration of TMAO is high enough, α-synuclein forms oligomers in which the subunits are folded and are not able to fibrillate. | Uversky V et al., 2001 |
TMAO: Trimethylamine N-oxide.; Aβ: Amyloid beta; ZO-1: Tight junction protein-1; PrPC: Scrapie prion protein.