Calcium homeostasis in aging neurons.

Nektarios Tavernarakis,Vassiliki Nikoletopoulou

doi:10.3389/fgene.2012.00200

Abstract

The nervous system becomes increasingly vulnerable to insults and prone to dysfunction during aging. Age-related decline of neuronal function is manifested by the late onset of many neurodegenerative disorders, as well as by reduced signaling and processing capacity of individual neuron populations. Recent findings indicate that impairment of Ca2+ homeostasis underlies the increased susceptibility of neurons to damage, associated with the aging process. However, the impact of aging on Ca2+ homeostasis in neurons remains largely unknown. Here, we survey the molecular mechanisms that mediate neuronal Ca2+ homeostasis and discuss the impact of aging on their efficacy. To address the question of how aging impinges on Ca2+ homeostasis, we consider potential nodes through which mechanisms regulating Ca2+ levels interface with molecular pathways known to influence the process of aging and senescent decline. Delineation of this crosstalk would facilitate the development of interventions aiming to fortify neurons against age-associated functional deterioration and death by augmenting Ca2+ homeostasis.

Highlights

Fluctuations in intracellular calcium concentration act as signals for a variety of processes in neurons
Ca2+ is the major trigger of neurotransmitter release, a process that has been thoroughly investigated over the past decades (Neher and Sakaba, 2008)
The ability of the N -methyl-D-aspartate (NMDA) receptor to act as a “coincidence receptor,” requiring the concomitant presence of its ligand and membrane depolarization in order to be activated, explains many aspects of its functional involvement in long-term potentiation (LTP) and synaptic plasticity, a process associated with memory and learning as discussed later

Summary

Vassiliki Nikoletopoulou and Nektarios Tavernarakis*

The impact of aging on Ca2+ homeostasis in neurons remains largely unknown. We survey the molecular mechanisms that mediate neuronal Ca2+ homeostasis and discuss the impact of aging on their efficacy. To address the question of how aging impinges on Ca2+ homeostasis, we consider potential nodes through which mechanisms regulating Ca2+ levels interface with molecular pathways known to influence the process of aging and senescent decline. Delineation of this crosstalk would facilitate the development of interventions aiming to fortify neurons against age-associated functional deterioration and death by augmenting Ca2+ homeostasis

INTRODUCTION

MECHANISMS OF NEURONAL CALCIUM HOMEOSTASIS RELEVANT TO AGING AND DEGENERATION

Nikoletopoulou and Tavernarakis

Golgi Mitochondria

Findings

EFFLUX OF CALCIUM THROUGH THE PLASMA MEMBRANE