Data di Pubblicazione:
2016
Citazione:
The Role of Cyclo(His-Pro) in Neurodegeneration / G. S., I. Ferrari, G. Pietrini, P. M., M. A., B. I.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 17:8(2016 Aug 12). [10.3390/ijms17081332]
Abstract:
Neurodegenerative diseases may have distinct genetic etiologies and pathological
manifestations, yet share common cellular mechanisms underpinning neuronal damage and
dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative
damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events
for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against
damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic
removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing
hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is
ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which
are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and,
once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-B
signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application
by both parenteral and oral administration routes and may represent an important new tool in
counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the
chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving
neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or
restore neuronal function.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
oxidative stress; endoplasmic reticulum stress; neuroinflammation
Elenco autori:
G. S., I. Ferrari, G. Pietrini, P. M., M. A., B. I.
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