[The role of extracellular α-synuclein in molecular mechanisms of cell death].

Recently published data demonstrated that increased release, oligomerization and toxicity of α-synuclein (ASN) is a key molecular process in pathophysiology of neurodegenerative diseases classified as synucleinopathies (e.g. Parkinson disease or Alzheimer's disease).

Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio.

Significance: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder mainly affecting elderly individuals. The pathology of AD is characterized by amyloid plaques (aggregates of amyloid-β [Aβ]) and neurofibrillary tangles (aggregates of tau), but the mechanisms underlying this dysfunction are still partially unclear.

Recent Advances: A growing body of evidence supports mitochondrial dysfunction as a prominent and early, chronic oxidative stress-associated event that contributes to synaptic abnormalities and, ultimately, selective neuronal degeneration in AD.

A novel mechanism of non-Aβ component of Alzheimer's disease amyloid (NAC) neurotoxicity. Interplay between p53 protein and cyclin-dependent kinase 5 (Cdk5).

The non-Aβ component of Alzheimer's disease (AD) amyloid (NAC) is produced from the precursor protein NACP/α-synuclein (ASN) by till now unknown mechanism. Previous study showed that like ASN, NAC peptide induced oxidative/nitrosative stress and apoptosis. Our present study focused on the mechanisms of PC12 cells death evoked by NAC peptide, with particular consideration on the role of p53 protein.

Alpha-synuclein induced cell death in mouse hippocampal (HT22) cells is mediated by nitric oxide-dependent activation of caspase-3.

Our previous studies indicated that exogenous alpha-synuclein (ASN) activates neuronal nitric oxide (NO) synthase (nNOS) in rat brain slices. The present study, carried out on immortalized hippocampal neuronal cells (HT22), was designed to extend the previous results by showing the molecular pathway of NO-mediated cell death induced by exogenous ASN. Extracellular ASN (10 microM) was found to stimulate nitric oxide synthase (NOS) and increase caspase-3 activity in HT22 cells, leading to poly(ADP-ribose) polymerase (PARP-1) cleavage.

Effect of N-methyl-D-aspartate (NMDA) receptor antagonists on alpha-synuclein-evoked neuronal nitric oxide synthase activation in the rat brain.

alpha-Synuclein (ASN), a small presynaptic protein that is abundant in the brain, is implicated in the pathogenesis of neurodegenerative disorders including Parkinson's and Alzheimer's disease. The central domain of alpha-synuclein, the non-amyloid beta component of the Alzheimer's disease amyloid (NAC) is probably responsible for its toxicity. However, the molecular mechanism of alpha-synuclein action remains largely elusive.

Alpha-synuclein inhibits poly (ADP-ribose) polymerase-1 (PARP-1) activity via NO-dependent pathway.

alpha-Synuclein (ASN) is a brain-enriched protein that functions as a molecular chaperone and regulator of the synaptic vesicle cycle. However, if ASN is overexpressed and in prefibrillar oligomeric forms it activates free radical formation and has been implicated in neurodegeneration. The nuclear target for the free radical cascade is poly (ADP-ribose) polymerase-1 (PARP-1), a DNA-binding enzyme and transcriptional regulator that decides on cell survival or death.

alpha-Synuclein enhances secretion and toxicity of amyloid beta peptides in PC12 cells.

alpha-Synuclein is the fundamental component of Lewy bodies which occur in the brain of 60% of sporadic and familial Alzheimer's disease patients. Moreover, a proteolytic fragment of alpha-synuclein, the so-called non-amyloid component of Alzheimer's disease amyloid, was found to be an integral part of Alzheimer's dementia related plaques. However, the role of alpha-synuclein in pathomechanism of Alzheimer's disease remains elusive.

Alpha-synuclein decreases arachidonic acid incorporation into rat striatal synaptoneurosomes.

In the present study we investigated the role of alpha-synuclein (ASN) and its fragment NAC in arachidonic acid (AA) turnover in the rat brain. Our data indicated that ASN (10 microM) inhibited [3H]AA incorporation into phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS) together with phosphatidic acid (PA) by 13%, 27% and 38%, respectively. NAC (10 microM) reduced [3H]AA incorporation into PC and PA + PS by 17% and 34%, respectively.

Cardiac troponin I after external electrical cardioversion for atrial fibrillation as a marker of myocardial injury--a preliminary report.

Background: It is uncertain whether external electrical cardioversion (CV) of atrial fibrillation (AF) can cause myocardial injury identifiable by troponin I (cTnI).

Aim: To examine whether external CV of AF can cause cTnI rise as measured with high-sensitivity assay, and to identify factors determining this elevation.

Methods: Patients with non-valvular AF selected for CV were included.

Inhibition of mitochondrial complex II affects dopamine metabolism and decreases its uptake into striatal synaptosomes.

The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The aim of our study was to determine the relationship between inhibition of mitochondrial complex II and dopamine (DA) metabolism and its transport into rat striatal synaptosomes after exposure to 3-NP. The study was carried out using spectrophotometric, radiochemical and HPLC methods.

Alpha-synuclein and its neurotoxic fragment inhibit dopamine uptake into rat striatal synaptosomes. Relationship to nitric oxide.

Alpha-synuclein (ASN), a 140-amino acid protein, is richly expressed in presynaptic terminals in the central nervous system, where it plays a role in synaptic vesicle function. However, if it is altered and accumulated it is involved in neurodegeneration as Parkinson's disease (PD). ASN contained 35-amino acid domain known as non-amyloid beta component of Alzheimer's disease amyloid (NAC) that is probably responsible for its aggregation and toxicity.

Opportunistic coryneform organisms--residents of human skin.

Opportunistic infections are usually caused by endogenic flora originated from physiological flora. In this context we studied coryneform bacteria recovered from deeper layers of epidermis of the forehead (278 isolates) and the back (196 isolates) of healthy men. It was observed that coryneform bacteria are in dynamic equilibrium with coagulase-negative staphylococci and they amount 4,7% of resident aerobic flora.

Bacteria forming a resident flora of the skin as a potential source of opportunistic infections.

Along with progress of medicine, contribution that opportunistic bacteria make in nosocomial infections increases. Coagulase-negative staphylococci are these multiresistant strains which often cause this kind of infections. But more and more frequently other genera of bacteria are isolated.