Objective To identify a novel biochemical marker that precedes clinical symptoms in Alzheimer disease (AD). Methods Using quantitative polymerase chain reaction techniques, we measured circulating cell‐free mitochondrial DNA (mtDNA) cerebrospinal fluid (CSF) from study participants, selected cohort of 282 subjects, who were classified according to their concentrations amyloid β 1–42 , total tau, and phosphorylated tau by the presence or absence dementia, into asymptomatic subjects at risk...

Abstract Background Emerging evidence indicates that impaired mitophagy-mediated clearance of defective mitochondria is a critical event in Alzheimer’s disease (AD) pathogenesis. Amyloid-beta (Aβ) metabolism and the microtubule-associated protein tau have been reported to regulate key components mitophagy machinery. However, mechanisms lead dysfunction AD are not fully deciphered. We previously shown intraneuronal cholesterol accumulation can disrupt autophagy flux, resulting low Aβ...

Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome interphase, is typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort damaged DNA into cytoplasm. In this study, we explored MS MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release cytoplasm telomere fragments enriched telomerase reverse transcriptase (hTERT), capping protein TRF2, double-strand breaks marked...

In mature neurons, the number of synapses is determined by a neuronal activity-dependent dynamic equilibrium between positive and negative regulatory factors. We hypothesized that pentraxin (NP1), proapoptotic protein induced low activity, could be regulator synapse density because it found in dystrophic neurites Alzheimer's disease-affected brains. Here, we report knockdown NP1 increases excitatory excitability cultured rat cortical neurons enhances drive long-term potentiation hippocampus...

BackgroundBoth idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own DNA (mtDNA) previous studies reported that the release of mtDNA is a biomarker disease.MethodsWe now investigated relationship between replication, transcription in fibroblasts from patients (iPD) Leucine-rich repeat kinase 2G2019S -associated (LRRK2-PD), using Selfie-digital PCR, method allows absolute quantification genomes transcripts.FindingsIn comparison...

Astrocytes are key elements of brain circuits that involved in different aspects the neuronal physiology relevant to functions. Although much effort is being made understand how biology astrocytes affects circuits, astrocytic network heterogeneity and plasticity still poorly defined. Here, we have combined structural functional imaging astrocyte activity recorded mice using Ca2+-modulated photoactivatable ratiometric integrator specific optostimulation glutamatergic pathways map...

Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with progression therapeutic response.To evaluate CSF concentrations mtDNA MS patients can serve a marker ongoing neuropathology helpful to differentiate between subtypes. To explore effect disease-modifying therapies on...

Alzheimer’s type dementia (AD) exhibits clinical heterogeneity, as well differences in disease progression, a subset of patients with diagnosis AD progresses more rapidly (rpAD) than the typical slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content cell-free mitochondrial DNA (cf-mtDNA) precedes signs AD. We have now investigated relationship between cf-mtDNA and other biomarkers to determine whether particular biomarker profile underlies different...

Mitochondrial function and dynamics are essential for neurotransmission, neural neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1-6 genes), located in X chromosome, encodes a new family of proteins localise to mitochondria, regulating mitochondrial trafficking. The evolved by retrotransposition Armc10 mRNA, which is present all vertebrates considered be ancestor gene. Here investigate genomic organisation, functions putative neuroprotective role...

Abstract Introduction Low content of cell‐free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker early stage Alzheimer's disease (AD), but whether mtDNA altered rapid neurodegenerative dementia such as Creutzfeldt‐Jakob unknown. Methods CSF was measured using digital polymerase chain reaction (dPCR) two independent cohorts comprising total 112 patients diagnosed with sporadic (sCJD), probable AD, or non‐Alzheimer's type dementia. Results Patients AD exhibit low compared...

In cultured cerebellar granule neurons, low neuronal activity triggers the intrinsic program of apoptosis, which requires protein synthesis-dependent BAX translocation to mitochondria, a process that may underlie damage in neurodegeneration. However, mechanisms link with induction mitochondrial apoptosis remain unclear. Neuronal pentraxin 1 (NP1) is pro-apoptotic induced by increased damaged neurites Alzheimer's disease-affected brains. Here we report NP1 facilitates accumulation...

Abstract Repeated cocaine exposure causes long‐lasting neuroadaptations that involve alterations in cellular signaling and gene expression mediated by dopamine different brain regions, such as the striatum. Previous studies have pointed out to D1 receptor one major player psychostimulants‐induced behavioral, cellular, molecular changes. However, role of other receptors has not been fully characterized. Here we used D2 knockout (D2 −/− ) mice explore (D2R) behavioral sensitization its...

Absolute measurement of the number RNA transcripts per gene is necessary to compare transcription among different tissues or experimental conditions and assess genes that have a variable copy cell such as mitochondrial DNA. Here, we present method called Selfie-digital PCR measures absolute amount an transcript produced by its own coding DNA at particular moment. Overcoming limitations previous approaches, allows for quantification nuclear in strand-specific manner comparable types differ...

Abstract Sporadic Alzheimer disease (SAD) is the most prevalent neurodegenerative disorder. With development of new generation DNA sequencing technologies, additional genetic risk factors have been described. Here we used various methods to process data in order gain further insight into this important disease. We sequenced exomes brain samples from SAD patients and non-demented controls. Using either method, found a higher number single nucleotide variants (SNVs), patients, genes present at...

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers premutation (55-200 CGG repeats) the fragile X mental retardation 1 (FMR1) gene. Several studies have shown mitochondrial dysfunction may play central role aging and also disorders such as Alzheimer's disease, Parkinson's Huntington's disease well FXTAS. It has been recently proposed mtDNA copy number, measured by number genomes per nuclear...

Colorectal cancer (CRC) can develop through several dysregulated molecular pathways, including the serrated pathway, characterized by CpG island methylator (CIMP) phenotype. Although tumor tissue is a commonly tested material, sample types such as stool or plasma, bring new, non-invasive approach. Several cancer-related methylated genes have been identified in CRC patients, gene GRIA4, showing promising diagnostic potential. The aim of our study was to sensitive droplet digital PCR (ddPCR)...