[5][10] The ectodomain was proposed to be cleaved to give a soluble peptide hormone named irisin.

This regulatory system is therefore investigated for potential interventions to improve cognitive function or alleviate Alzheimer's disease.

[22][23][24] The FNDC5 gene encodes a prohormone, a single-pass type I membrane protein (human, 212 amino acids; mouse and rat, 209 amino acids) that is upregulated by muscular exercise and undergoes post-translational processing to generate irisin.

The production of irisin is similar to the shedding and release of other hormones and hormone-like polypeptides, such as epidermal growth factor and TGF alpha, from transmembrane precursors.

[11][12][26] While this proposal has been challenged[27] by evidence finding FNDC5 is upregulated only in highly active elderly humans,[18] more recent literature has supported the hypothesis of FNDC5 and irisin having a necessary role in exercise related benefits.

[30] Irisin was shown to be a critical regulator of beneficial cognitive effects of physical exercise in rodents.

The vitality of these primary hippocampal nerve cells from diabetic rats was markedly decreased when BDNF levels were low but improved following irisin treatment.

Thus, irisin was found to positively regulate the expression of BDNF and negatively influence the levels of GHbA1c (human glycated hemoglobin A1c) and AGEs, suggesting that irisin influences cognitive dysfunction in rats with type 2 diabetes by regulating the expression of BDNF and glycometabolism.