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Editorial
. 2011 Feb;69(2):221-5.
doi: 10.1002/ana.22359.

Apomorphine and Alzheimer Aβ: roles for regulated α cleavage, autophagy, and antioxidation?

John W Steele, Sam Gandy
Editorial

Apomorphine and Alzheimer Aβ: roles for regulated α cleavage, autophagy, and antioxidation?

John W Steele et al. Ann Neurol. 2011 Feb.
No abstract available

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Figures

Figure 1
Figure 1. Schematic diagram of APP metabolism by cognate enzymes
Mature APP (center) is metabolized by two competing pathways, which generate “non-amyloidogenic” (left) and “amyloidogenic” (right) byproducts. Primary APP metabolism by α-secretase destroys Aβ and therefore precludes Aβ generation, aggregation, and related neurodegeneration. Processing of APP by β-secretase generates the C99 CTF, a γ-secretase substrate from which the neurotoxic 37-44 aminoacid Aβ peptide is derived. Aβ aggregates into low-n multimers (dimers, trimers, etc) known as oligomers, which have been associated with potent mnemonotoxicity. The current focus on oligomer toxicity predict that the senile plaque may be a relatively inert, endstage structure. (Figure is reprinted from with permission of The Journal of Clinical Investigation).
Figure 2
Figure 2. Immunoperoxidase and immunoelectron microscopy reveals APP/Aβ-LIR in intraneuronal organelles in the cerebral neurons of APPE693Q overexpressing transgenic mice
(Left and center) Intraneuronal vesicles are identifiable with monoclonal antibodies against two different Aβ epitopes. (Right) Immunoelectron microscopy using anti-rab5 shows that APP/Aβ-LIR is associated with small-, medium-, and large-sized cytoplasmic vesicular structures (including multivesicular bodies, dense lysosomes and lipofuscin). Interestingly, despite the absence of plaques, TgAPPE693Q accumulate oligomeric Aβ assemblies, intraneuronal APP/Aβ-LIR in the hippocampi and cerebral cortices, and impaired performance of the Morris water maze task (Figure is reprinted with permission from Annals of Neurology).
See this image and copyright information in PMC

Comment on

References

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