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Calcium is a key signaling ion involved in many different intracellular and extracellular processes ranging from synaptic activity to cell-cell communication and adhesion. The exact definition at the molecular...
The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secreta...
Tau protein exists as six different isoforms that differ by the inclusion or exclusion of exons 2, 3 and 10. Exon 10 encodes a microtubule binding repeat, thereby resulting in three isoforms with three microtu...
The low-density lipoprotein receptor-related protein 1 (LRP1) plays critical roles in lipid metabolism, cell survival, and the clearance of amyloid-β (Aβ) peptide. Functional soluble LRP1 (sLRP1) has been dete...
Autophagy is the major pathway involved in the degradation of proteins and organelles, cellular remodeling, and survival during nutrient starvation. Autophagosomal dysfunction has been implicated in an increas...
In AtT-20 cells ACTH secretion is regulated by both Ca2+ and G proteins. We previously demonstrated that calnuc, an EF-hand Ca2+ binding protein which regulates Alzheimer's β-amyloid precursor protein (APP) bioge...
Accumulating evidence suggests that neurons prone to degeneration in Alzheimer's Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a g...
Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, ...
Mutations in the DJ-1 gene have been linked to autosomal recessive familial Parkinson's disease. To understand the function of DJ-1, we determined the DJ-1 expression in both zebrafish and post mortem human br...
Expansion of a polyglutamine repeat at the amino-terminus of huntingtin is the probable cause for Huntington's disease, a lethal progressive autosomal-dominant neurodegenerative disorders characterized by impa...
Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestat...
α-Synuclein is a small protein that has special relevance for understanding Parkinson disease and related disorders. Not only is α-synuclein found in Lewy bodies characteristic of Parkinson disease, but also m...
Despite major advances in our understanding of the initiating factors that trigger many neurodegenerative disorders, to date, no novel disease-modifying therapies have been shown to provide significant benefit...
Midbrain dopaminergic neurons are involved in control of emotion, motivation and motor behavior. The loss of one of the subpopulations, substantia nigra pars compacta, is the pathological hallmark of one of th...
Gene microarray technology is an effective tool to investigate the simultaneous activity of multiple cellular pathways from hundreds to thousands of genes. However, because data in the colossal amounts generat...
Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc-metalloprotease that degrades several pathophysiologically significant extracellular substrates, including insulin and the amyloid β-protein (Aβ)...
Huntington's disease (HD) is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabol...
The amyloid β-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine A...
Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxi...
Insulin degrading enzyme (IDE) is implicated in the regulation of amyloid β (Aβ) steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's dise...
Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of ...
Mutations in the presenilin (PSEN) genes are associated with early-onset familial Alzheimer's disease (FAD). Biochemical characterizations and comparisons have revealed that many PSEN mutations alter γ-secretase ...
Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease post-mortem. Genetic variability in SNCA cont...
Chondroitin sulphate proteoglycan (NG2) expressing cells, morphologically characterized by multi-branched processes and small cell bodies, are the 4th commonest cell population of non-neuronal cell type in the ce...
Transcriptional dysregulation is an early, key pathogenic mechanism in Huntington's disease (HD). Therefore, gene expression analyses have biomarker potential for measuring therapeutic efficacy in pre-clinical...
The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephri...
Dimebon is an antihistamine compound with a long history of clinical use in Russia. Recently, Dimebon has been proposed to be useful for treating neurodegenerative disorders. It has demonstrated efficacy in ph...
Familial Alzheimer's disease-linked variants of presenilin (PSEN1 and PSEN2) contribute to the pathophysiology of disease by both gain-of-function and loss-of-function mechanisms. Deletions of PSEN1 and PSEN2 in ...
Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-β plaques, ne...
Regulated intramembrane proteolysis of the β-amyloid precursor protein by the γ-secretase yields two peptides. One, amyloid-β, is the major component of the amyloid plaques found in Alzheimer's disease patient...
The physiological function of the cellular prion protein (PrPC) remains unknown. However, PrPC has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic s...
A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in APP regulatory sequences, can lead to development of early-onset dementias, including A...
Recent evidence supports a neuroprotective role for Wnt signaling in neurodegenerative disorders such as Alzheimer's Disease (AD). In fact, a relationship between amyloid-β-peptide (Aβ)-induced neurotoxicity and ...
Abnormalities of microtubule-associated protein tau play a central role in neurofibrillary degeneration in several neurodegenerative disorders that collectively called tauopathies. Six isoforms of tau are expr...
Experimental autoimmune encephalomyelitis (EAE) is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS). Four distinct autoimm...
Presenilin (PS1 or PS2) is an essential component of the active γ-secretase complex that liberates the Aβ peptides from amyloid precursor protein (APP). PS1 is regarded as an atypical aspartyl protease harbori...
Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived...
Alterations in multiple cellular pathways contribute to the development of chronic neurodegeneration such as a sporadic Alzheimer's disease (AD). These, in turn, involve changes in gene expression, amongst whi...
Parkinson's disease (PD) is the most prevalent incurable neurodegenerative movement disorder. Mutations in LRRK2 are associated with both autosomal dominant familial and sporadic forms of PD. LRRK2 encodes a larg...
The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to gen...
The early stages of Alzheimer's disease (AD) are closely associated with the production of the Aβ1–42 peptide, loss of synapses and gradual cognitive decline. Since some epidemiological studies showed that EGb 76...
Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such ...
The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the β-amyloid peptide are hallmark neuropathological lesions in Alzh...
Mice carrying the spontaneous genetic mutation known as Wallerian degeneration slow (Wld s ) have a unique neuroprotective phenotype, where axonal and synaptic compartments o...
Recent studies demonstrate that in addition to its modulatory effect on APP processing, in vivo application of Liver X Receptor agonist T0901317 (T0) to APP transgenic and non-transgenic mice decreases the level ...
Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell lin...
The Retraction Note to this article has been published in Molecular Neurodegeneration 2009 4:45
Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insolu...
Alzheimer's disease (AD) is characterized by the presence of two histopathological hallmarks; the senile plaques, or extracellular deposits mainly composed of amyloid-β peptide (Aβ), and the neurofibrillary ta...
The strain of MeCP2tm1.1Bird mice is a broadly used model for Rett syndrome. Because males carrying the invalidated MeCP2 locus are sterile, this strain has to be maintained in a heterozygous state. All animals t...
Molecular Neurodegeneration