Increased proteolytic activity is a hallmark of several pathological processes, including neurodegeneration. Recent studies reveal that a disturbed balance of their enzymatic activities is the first insult in brain aging and age-related diseases. The proteolytic activity of cysteine cathepsins is controlled by endogenous protein inhibitors which evidently fail to perform their function in neurodegenerative processes. Exogenous synthetic inhibitors, which may augment their inhibitory potential, are considered as possible therapeutic tools for the treatment of neurological disorders.
COBISS.SI-ID: 3559025
Gama-enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C-terminal end of the molecule. We have investigated the expression and co-localization of gama-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. Gamma enolase intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque and was proved to be neuroprotective against Aß toxicity.
COBISS.SI-ID: 3441265
Gama-enolase exerts a protective effect against amyloid-ß-peptide (Aß)-induced neurotoxicity in PC12 cells. Aß-induced toxicity was abolished in the presence of the active C-terminal peptide of gamma-enolase, which caused downregulation of the pro-apoptotic protein Bax and upregulation of the anti-apoptotic protein Bcl-2, as well as reduced caspase-3 activation. Exposure to Aß increased surface expression of p75 neurotrophin receptor (p75NTR), and the pretreatment with gamma enolase peptide suppressed the activation of mitogen-activated protein kinases p38 and Jun-N-terminal kinase, which are p75NTR downstream effectors in apoptotic signaling. Gamma enolase also colocalized with p75NTR. Our results indicate the possible use of gama enolase C-terminal peptide for treating or preventing Alzheimer's disease.
COBISS.SI-ID: 3492209
Gama-Enolase, a glycolytic enzyme, is expressed specifically in neurons. It exerts neurotrophic activity and has been suggested to regulate growth, differentiation, survival and regeneration of neurons. In this study, we investigated the involvement of gama enolase in PI 3-kinase/Akt) and MAPK/ERK (mitogen-activated protein kinase/ extracellular-signal-regulated kinase) signaling, the two pathways triggered predominantly by neurotrophic factors. While the PI 3-K/Akt pathway, rather than the MAPK/ERK pathway, is involved in gama-enolase-enhanced cell survival, gama-enolase-stimulated neurite outgrowth requires both pathways, i.e. the activation of both PI 3-K and ERK1/2, leading to subsequent expression of growth cone-specific GAP-43 protein.
COBISS.SI-ID: 3194993