... of Alzheimer's disease (AD) where the role of human PSEN1 and PSEN2 is well known. Summary:   PSEN, Endo16, Wnt5, Hnf6 and Gsc are transcribed in both the sense and antisense directions in the sea urchin. A general control of the sense-antisense transcription could be crucial for correct embryonic...

... are an early event in Alzheimer's disease (AD) pathogenesis. However, the mechanisms underlying these abnormalities are unclear. The transient receptor potential channel mucolipin 1(TRPML1, also known as MCOLN1), a vital endosomal-lysosomal Ca 2+ channel whose loss of function leads to neurodegeneration, has...

...Kazuhito Sai; Aoi Nakanishi; Kimberly M. Scofield; Debra A. Tokarz; Keith E. Linder; Todd J. Cohen; Jun Ninomiya-Tsuji ABSTRACT Neuroinflammation is causally associated with Alzheimer's disease (AD) pathology. Reactive glia cells secrete various neurotoxic factors that impair neuronal homeostasis...

..., many are now entering the prime age when Alzheimer's disease (AD)-like symptoms begin to manifest. It has been shown that hyperphosphorylated tau, a known AD pathological characteristic, is prematurely increased in the brains of HIV-infected individuals as early as in their 30s and that its levels...

...Gianna M. Fote; Nicolette R. Geller; Nikolaos E. Efstathiou; Nathan Hendricks; Demetrios G. Vavvas; Jack C. Reidling; Leslie M. Thompson; Joan S. Steffan ABSTRACT The human apolipoprotein E4 isoform (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), and lysosomal...

... in the brain, an interaction disturbed by apoE4, the major risk factor for sporadic Alzheimer's disease. Alzheimer's disease Fatty acid binding protein Polyunsaturated fatty acid Protein sorting VPS10P domain receptor European Research Council http://dx.doi.org/10.13039/100010663 BeyOND...

..., contributing to the pathophysiology of Alzheimer's disease. In this Review, we discuss the principles of the ‘nuclear calcium hypothesis’ in the context of human brain function and its role in controlling diverse forms of neuroadaptation and neuroprotection. Furthermore, we present the most relevant...

...Natasha Vassileff; Lesley Cheng; Andrew F. Hill ABSTRACT Neurodegenerative diseases are characterised by the irreversible degeneration of neurons in the central or peripheral nervous systems. These include amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD...

... the characterization of mRNAs encoding GFAP-α and GFAP-δ isoforms as a proof of concept, we showed that they mainly localized on GFAP processes. In the APPswe/PS1dE9 mouse model of Alzheimer's disease, the density and distribution of both α and δ forms of Gfap mRNA changed as a function of the region...

... that dual inhibition of the SHIP1 and 2 paralogs can provide a novel means to enhance basal microglial homeostatic functions for therapeutic purposes in Alzheimer's disease and, possibly, other types of dementia where increased microglial function could be beneficial. * These authors contributed...

... hippocampal cultures and adult mouse brain. Finally, SHP2 levels were upregulated in samples from patients with mild and severe Alzheimer's disease (AD), and the level of tau–SHP2 complexes were increased in AD patient samples. These findings strongly suggest a role for the tau–SHP2 interaction in NGF...

...Dina S. Coelho; Eduardo Moreno ABSTRACT Alzheimer's disease (AD) causes a progressive loss of memory and other cognitive functions, which inexorably debilitates patients. There is still no cure for AD and effective treatments to delay or revert AD are urgently needed. On a molecular level...

...Kumar Nikhil; Kavita Shah ABSTRACT Cdk5 deregulation is highly neurotoxic in Alzheimer's disease (AD). We identified Mcl-1 as a direct Cdk5 substrate using an innovative chemical screen in mouse brain lysates. Our data demonstrate that Mcl-1 levels determine the threshold for cellular damage...

... ABSTRACT Dysfunction and loss of synapses are early pathogenic events in Alzheimer's disease. A central step in the generation of toxic amyloid-β (Aβ) peptides is the cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). Here, we have elucidated whether downregulation of septin...

...Xu Yan; Niko-Petteri Nykänen; Cecilia A. Brunello; Annakaisa Haapasalo; Mikko Hiltunen; Riikka-Liisa Uronen; Henri J. Huttunen ABSTRACT One of the defining pathological features of Alzheimer's disease is the intraneuronal accumulation of tau (also known as MAPT) protein. Tau is also secreted from...

...Chun Shi; Keith Viccaro; Hyoung-gon Lee; Kavita Shah ABSTRACT Deregulated Cdk5 causes neurotoxic amyloid beta peptide (Aβ) processing and cell death, two hallmarks of Alzheimer's disease, through the Foxo3 transcriptional factor in hippocampal cells, primary neurons and an Alzheimer's disease mouse...

...James R. Edgar; Katarina Willén; Gunnar K. Gouras; Clare E. Futter ABSTRACT Intracellular amyloid-β (Aβ) accumulation is a key feature of early Alzheimer's disease and precedes the appearance of Aβ in extracellular plaques. Aβ is generated through proteolytic processing of amyloid precursor protein...

...Valérie Vingtdeux; Pallavi Chandakkar; Haitian Zhao; Lionel Blanc; Santiago Ruiz; Philippe Marambaud ABSTRACT Alzheimer's disease is characterized by amyloid-β (Aβ) peptide accumulation in the brain. CALHM1, a cell-surface Ca 2+ channel expressed in brain neurons, has anti-amyloidogenic properties...

... defective autophagy in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease and Huntington's disease. Recent work using live-cell imaging has identified autophagy as a predominantly polarized process in neuronal axons; autophagosomes...

... neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control...