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Nervous system growth factors have extensive effects on neuronal function and survival. Nerve growth factor (NGF) prevents the death and stimulates the function of basal forebrain cholinergic neurons in correlational models of Alzheimer’s disease (AD), leading to its translation to Phase 1 and 2 human clinical trials. Separately, Brain-Derived Neurotrophic Factor (BDNF) infl uences the survival and...
Proteasome is a multi-activity enzyme involved in a ubiquitin-dependent turnover of cytoplasmic and nuclear proteins. It recognizes and digests short-lived regulatory proteins, influencing cellular processes as crucial as progression of the cell cycle, transcription, oncogenesis and flux of substrates through metabolic pathways. The enzyme is responsible also for the housekeeping chores, degrading...
Aging is accompanied by a high level of oxidized form of guanine, 8-oxo-2’deoxyguanosine (8-oxo-2’dG), and decreased level of 8-oxoguanine glycosylase 1 (OGG1) in the brain. The development and progression of neurodegenerative disorders are also characterized by dysfunction or loss of the brain nicotinic acetylcholine receptors (nAChRs). To study whether the differences in nAChRs expression in the...
Alpha-Synuclein (ASN), a small cytosolic protein enriched in synaptic terminals, was implicated in the pathomechanism of several neurodegenerative disorders called alpha-synucleinopathies. ASN was shown to be a main component of characteristic intraneuronal protein aggregates called Lewy bodies (LB) and Lewy neurites (LN), observed i.a. in Parkinson’s disease, dementia with LBs and in the LB variant...
Sphingolipid deregulation may be an important factor of age-related neuronal stress vulnerability. Current data suggests potential links between sphingosine kinases (SphK1&2), their product sphingosine1-phosphate (S1P) and age-related protein conformation diseases. The aim of this study was to investigate a possible role of SphKs in alpha-synuclein (ASN) and amyloid beta (ABeta) precursor protein...
alpha-Synuclein (ASN) play important role in pathogenesis of Parkinson’s disease (PD) and other neurodegenerative disorders. Novel and most interesting data showed elevated tauopathy in PD and suggested relationship between ASN and Tau protein. However, the mechanism of ASN-evoked Tau protein modification is not fully elucidated. In this study, we investigated the role of glycogen synthase kinase-3β...
Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and induce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived...
Basic research into neurodegenerative disorders, like Alzheimer’s disease, is heavily focused on understanding genetic susceptibility and biochemical triggers of pathology, as well as disturbances to the intrinsic electrophysiological properties of affected neurons. Often overlooked is the role of mechanics, particularly mechanical properties and mechano‑sensitivity/‑responsiveness of neurons and...
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