Neuropeptide Kyotorphin (Tyrosyl-Arginine) has Decreased Levels in the Cerebro-Spinal Fluid of Alzheimer’s Disease Patients: Potential Diagnostic and Pharmacological Implications

Abstract

In Alzheimer’s disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endogenous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible correlation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured. We found a statistically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection.

Benzoyl chloride derivatization with liquid chromatography–mass spectrometry for targeted metabolomics of neurochemicals in biological samples

“…Kyotorphin is an endogenous analgesic dipeptide with potential neuroprotective properties. It has previously been found in rat brain tissue and human CSF samples [57, 58]. This is the first report of quantitative detection of kyotorphin in human serum.…”

“…Kyotorphin is proposed to have indirect opioid-like actions by modulating enkephalin release [59]. Kyotorphin does not cross the blood brain barrier, and is a candidate biomarker for neurodegenerative diseases such as Alzheimer’s disease [57]. While previous studies detected kyotorphin in CSF samples obtained from lumbar puncture, less invasive blood sample collection would be beneficial for patients, with subsequent detection as reported here.…”

Cerebrospinal fluid biomarkers of Alzheimer’s disease

“…Santos et al reported that it has an inverse correlation with p-tau, and that p-tau/KTP values differ significantly between AD cases and controls [80] . Thus, KTP has potential utility in diagnosing AD.…”

Possible Anti-Stressor Effects of Kyotorphin and its Optical Isomer

“…Concerning the penetration of Blood-Brain Barrier (BBB) of KTP, the literature data are contradictory. The majority of research associated with KTP claimed that it has limited capacity to cross the BBB 48 . Some literature data showed that KTP was transported by H + -coupled peptide transporter PEPT2 [49][50][51][52] .…”