Aging and disease

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01 January 2010. VOL 1, ISSUE 1 Next Issue

Editorial

A&D, a bridge between aging and age-related disease
Kunlin Jin, Ashok K. Shetty and David A. Greenberg

2010, 1 (1): 1-1
Reelin Signaling, Hippocampal Neurogenesis, and Efficacy of Aspirin Intake & Stem Cell Transplantation in Aging and Alzheimer’s disease
Ashok K. Shetty

2010, 1 (1): 2-11

PDF (382KB)
Reelin-mediated Signaling during Normal and Pathological Forms of Aging
Jana Doehner, Irene Knuesel

2010, 1 (1): 12-29

PDF (1482KB)
Memory and Neurogenesis in Aging and Alzheimer’s Disease
Jesus Avila, Ricardo Insausti, Joaquin Del Rio

2010, 1 (1): 30-36

PDF (357KB)
Alzheimer’s Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin
Massimo F. L. Pomponi, Giovanni Gambassi, Massimiliano Pomponi, Carlo Masullo

2010, 1 (1): 37-59

PDF (1008KB)
Stem Cell Transplantation for Enhancement of Learning and Memory in Adult Neurocognitive Disorders
Ben Waldau

2010, 1 (1): 60-71

PDF (419KB)

Cover Illustration

01 January 2010. Vol.1 No.1
Hypothetical model how dysfunctional Reelin-mediated signaling may induce pathological aging. In the course of normal aging, Reelin accumulates in the extracellular matrix either as monomers, dimers, or oligomers and/or cleaved fragments, which are efficiently cleared by activated astrocytes and microglia [39, 108]. Long-term imbalances in immune modulators including elevated levels of pro-inflammatory cytokines in old subjects increase the expression of metalloproteinases, resulting in aberrant cleavage of extracellular Reelin and production of an excess of Reelin fragments. While N-terminal fragments might preferentially aggregate in concert with proteolytic APP fragments [105], the central fragments are expected to compete with full-length Reelin homodimers for the available receptors to inhibit Reelin downstream signaling. Dysfunctional Reelin signaling is expected to promote not only amyloidogenic APP processing [7, 19, 111] including the production of N-APP, and Tau hyperphosphorylation [16, 24, 25, 137], it likely also impairs synaptic plasticity [28, 45, 52] via the strong reduction of several Reelin-mediated downstream signaling cascades required for proper neuronal functioning. NFT = Neurofibrillary tangles. Thin arrows represent downregulation; thick arrows indicate an up-regulation compared to the normal signaling pathways described during development and adult synaptic functions.

[Detail]

Cover Illustration

Hypothetical model how dysfunctional Reelin-mediated signaling may induce pathological aging. In the course of normal aging, Reelin accumulates in the extracellular matrix either as monomers, dimers, or oligomers and/or cleaved fragments, which are efficiently cleared by activated astrocytes and microglia [39, 108]. Long-term imbalances in immune modulators including elevated levels of pro-inflammatory cytokines in old subjects increase the expression of metalloproteinases, resulting in aberrant cleavage of extracellular Reelin and production of an excess of Reelin fragments. While N-terminal fragments might preferentially aggregate in concert with proteolytic APP fragments [105], the central fragments are expected to compete with full-length Reelin homodimers for the available receptors to inhibit Reelin downstream signaling. Dysfunctional Reelin signaling is expected to promote not only amyloidogenic APP processing [7, 19, 111] including the production of N-APP, and Tau hyperphosphorylation [16, 24, 25, 137], it likely also impairs synaptic plasticity [28, 45, 52] via the strong reduction of several Reelin-mediated downstream signaling cascades required for proper neuronal functioning. NFT = Neurofibrillary tangles. Thin arrows represent downregulation; thick arrows indicate an up-regulation compared to the normal signaling pathways described during development and adult synaptic functions.