Activity-dependent neuroprotector homeobox protein: A candidate protein identified in serum as diagnostic biomarker for Alzheimer's disease

2012 ◽  
Vol 75 (12) ◽  
pp. 3617-3629 ◽  
Author(s):  
Ming-Hui Yang ◽  
Yuan-Han Yang ◽  
Chi-Yu Lu ◽  
Shiang-Bin Jong ◽  
Li-Jhen Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein A ◽  
Diagnostic Biomarker ◽  
Homeobox Protein ◽  
Candidate Protein ◽  
Activity Dependent

scholarly journals Activity-dependent neuroprotector homeobox protein level in Alzheimer's disease in Taiwanese

2012 ◽  
Vol 4 (1-2) ◽  
pp. 48-50 ◽  
Author(s):  
Yu-Fen Lin ◽  
Ming-Hui Yang ◽  
Yuan-Han Yang ◽  
Wen-Cheng Chen ◽  
Chi-Yu Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Level ◽  
Homeobox Protein ◽  
Activity Dependent

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

scholarly journals E22Δ Mutation in Amyloidβ-Protein Promotesβ-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Takayuki Suzuki ◽  
Kazuma Murakami ◽  
Naotaka Izuo ◽  
Toshiaki Kume ◽  
Akinori Akaike ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Conformational Change ◽  
Deletion Mutant ◽  
Protein A ◽  
Type A ◽  
Synaptic Dysfunction ◽  
Wild Type ◽  
Radical Production

Oligomers of 40- or 42-mer amyloidβ-protein (Aβ40, Aβ42) cause cognitive decline and synaptic dysfunction in Alzheimer's disease. We proposed the importance of a turn at Glu22 and Asp23 of Aβ42 to induce its neurotoxicity through the formation of radicals. Recently, a novel deletion mutant at Glu22 (E22Δ) of Aβ42 was reported to accelerate oligomerization and synaptotoxicity. To investigate this mechanism, the effects of the E22Δ mutation in Aβ42 and Aβ40 on the transformation ofβ-sheets, radical production, and neurotoxicity were examined. Both mutants promotedβ-sheet transformation and the formation of radicals, while their neurotoxicity was negative. In contrast, E22P-Aβ42 with a turn at Glu22 and Asp23 exhibited potent neurotoxicity along with the ability to form radicals and potent synaptotoxicity. These data suggest that conformational change in E22Δ-Aβis similar to that in E22P-Aβ42 but not the same, since E22Δ-Aβ42 exhibited no cytotoxicity, unlike E22P-Aβ42 and wild-type Aβ42.

scholarly journals Formation of Toxic Amyloid Fibrils by Amyloidβ-Protein on Ganglioside Clusters

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Katsumi Matsuzaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Physicochemical Properties ◽  
Lipid Rafts ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Protein A ◽  
Pivotal Role ◽  
Membrane Interaction

It is widely accepted that the conversion of the soluble, nontoxic amyloidβ-protein (Aβ) monomer to aggregated toxic Aβrich inβ-sheet structures is central to the development of Alzheimer’s disease. However, the mechanism of the abnormal aggregation of Aβin vivo is not well understood. Accumulating evidence suggests that lipid rafts (microdomains) in membranes mainly composed of sphingolipids (gangliosides and sphingomyelin) and cholesterol play a pivotal role in this process. This paper summarizes the molecular mechanisms by which Aβaggregates on membranes containing ganglioside clusters, forming amyloid fibrils. Notably, the toxicity and physicochemical properties of the fibrils are different from those of Aβamyloids formed in solution. Furthermore, differences between Aβ-(1–40) and Aβ-(1–42) in membrane interaction and amyloidogenesis are also emphasized.

scholarly journals Microtubule assembly by soluble tau impairs vesicle endocytosis and excitatory neurotransmission via dynamin sequestration in Alzheimer's disease synapse model

2021 ◽  
Author(s):  
Tetsuya Hori ◽  
Kohgaku Eguchi ◽  
Han-Ying Wang ◽  
Tomohiro Miyasaka ◽  
Laurent Guillaud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo ◽  
Microtubule Assembly ◽  
Pleckstrin Homology Domain ◽  
Endocytic Protein ◽  
Brainstem Slices ◽  
Excitatory Neurotransmission ◽  
Synapse Model ◽  
Activity Dependent

Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer's disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in brainstem slices. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10-20 μM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin-1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission.

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