Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER
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TaubCONNECT Research Perspectives:
February 2015



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#1 Dysregulation of microRNA-219 promotes neurodegeneration through
     post-transcriptional regulation of tau

#2 Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban
     community

#3 Increased permeability-glycoprotein inhibition at the human blood-brain
     barrier can be safely achieved by performing PET during peak plasma
     concentrations of tariquidar

» Regulation of synaptic plasticity and cognition by SUMO in normal physiology and
   Alzheimer's disease


» Lobar Microbleeds Are Associated with a Decline in Executive Functioning in
   Older Adults

» Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

» Inbreeding among Caribbean Hispanics from the Dominican Republic and its effects on
   risk of Alzheimer disease

» Coding mutations in SORL1 and Alzheimer's disease

First Place: Pathogenic Role of Formin-mediated Stable Detyrosinated
     Microtubule Inductionby Amyloid beta

First Place: Differential responsiveness to entorhinal cortical input distinguishes CA1
    pyramidal neuron subpopulations

» Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients,
   independent of cortical plaque severity

» A Time Course Analysis of the Electrophysiological Properties of Neurons Differentiated
   from Human Induced Pluripotent Stem Cells (iPSCs)

» Axonally Synthesized ATF4 Transmits a Neurodegenerative Signal across Brain Regions

» Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging
   and Alzheimer's Disease

» Neurological disorders: Quality-control pathway unlocked

» Estrogen Receptor ╬▒ Variants Modify Risk for Alzheimer's Disease in a Multiethnic
   Female Cohort

» Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from
   apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT
   signalling and Guidelines

» Local synthesis of TC10 is required for membrane expansion during axon outgrowth

» Biobanked Alzheimer's Brain Tissue Yields Living Neurons

» Behavioral Assays with Mouse Models of Alzheimer's Disease: Practical Considerations
   and Guidelines

» Biobanked Alzheimer's Brain Tissue Yields Living Neurons

» Picomolar Amyloid-╬▓ Peptides Enhance Spontaneous Astrocyte Calcium Transients



Neurotherapeutics: Rethinking Alzheimer's Disease Therapies

What follows are a selection of articles, authored or co-authored by Taub faculty, from a special issue of the journal Neurotherapeutics. The complete volume features additional reviews and original contributions from investigators at various institutions and is available online.

An excerpt from the opening editorial, Stuck in the Mire, by guest editors Drs. Michael Shelanski and Roger Lefort explains:

"The articles in this volume focus on a number of systems that are affected in AD. They explore key topics such as energetics and mitochondria, the role of heavy metals, molecules to increase synaptic plasticity and approaches to the defects in protein sorting and in protein degradation. Given the limitations mentioned in current animal models, articles in this volume describe advances in the use of human stem cells and stem cell-derived neurons for the study of AD, as well as the application of the new areas of computational and systems biology to analyze data derived from post-mortem human brain to predict master regulators of AD progression.

The sum total of the articles provides a snapshot of where we are at this place and time, the model systems that might be appropriate and some glimpse of future research directions" (2).

The Use of Pharmacological Retromer Chaperones in Alzheimer's Disease and other Endosomal-related Disorders
Diego E. Berman, Dagmar Ringe, Greg A. Petsko, Scott A. Small
Pages 12-18

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders
Roger Lefort
Pages 19-28

Synaptic Therapy in Alzheimer's Disease: A CREB-centric Approach
Andrew F. Teich, Russell E. Nicholls, Daniela Puzzo, Jole Fiorito, Rosa Purgatorio, Mauro Fa', Ottavio Arancio
Pages 29-41

Caspases: Therapeutic Targets in Neurologic Disease
Carol M. Troy, Ying Y. Jean
Pages 42-48

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration
Jimena Baleriola, Ulrich Hengst
Pages 57-65

Promoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease
Lauren G. Friedman, Yasir H. Qureshi, Wai Haung Yu
Pages 94-108

A Systems Approach to Drug Discovery in Alzheimer's Disease
Michael Shelanski, William Shin, Soline Aubry, Peter Sims, Mariano J. Alvarez, Andrea Califano
Pages 126-131

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease
Tae-Wan Kim
Pages 132-142

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