Beyond Aβ and tau: other toxic insults and AD pathology

Retromer in Alzheimer disease, Parkinson disease and other neurological disorders.

Scott A. Small and Gregory A. Petsko

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Tim Spencer
Senior Editor, Nature Neuroscience
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As discussed in the forum (see video here), there are many cellular pathways which are believed to be perturbed in Alzheimer’s Disease. Recent work has suggested that deficits in retromer complex function may underlie impairment of endosomal trafficking in neurons and may contribute to AD pathogenesis. This recent review illustrates the function of the retromer complex and discusses how its dysfunction may contribute to neurodegeneration.

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Nat Rev Neurosci. 2015 Mar;16(3):126-32. doi: 10.1038/nrn3896.

Also, see these selected papers for more on some of the different cellular processes which may influence AD pathogenesis:

Neurobiol Aging. 2011 Nov;32(11):2109.e1-14. doi: 10.1016/j.neurobiolaging.2011.05.025.
Altered intrinsic neuronal excitability and reduced Na+ currents in a mouse model of Alzheimer's disease.
Brown JT, Chin J, Leiser SC, Pangalos MN, Randall AD.

Trends Neurosci. 2013 Jun;36(6):325-35. doi: 10.1016/j.tins.2013.03.002.
Why size matters - balancing mitochondrial dynamics in Alzheimer's disease.
DuBoff B, Feany M, Götz J.

Neuron. 2014 Dec 3;84(5):1023-33. doi: 10.1016/j.neuron.2014.10.024.
Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease.
Šišková Z, Justus D, Kaneko H, Friedrichs D, Henneberg N, Beutel T, Pitsch J, Schoch S, Becker A, von der Kammer H, Remy S.

Go to the profile of Tim Spencer

Tim Spencer

Senior Editor, Nature Neuroscience

Tim Spencer received his PhD from the City University of New York, where he studied the signaling mechanisms which underlie the promotion of axonal growth and regeneration following injury in the laboratory of Marie Filbin. He then moved to the laboratory of Chris Henderson at Columbia University, where he examined molecular markers of postnatal motor neuron maturation and elements of neurodegenerative diseases such as ALS and SMA. His research interests include neuronal development and maturation, axonal guidance and models of neuronal disease and dysfunction. Tim joined the editorial team of Nature Neuroscience in March of 2011, where he handles many of the manuscripts on neural development and neurogenesis, neurodegeneration, neuroinflammation and neuroimmune interactions, myelination/remyelination, molecular and cellular pathways, and "brain cancer" (glioblastoma, etc.).

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