The Na+/Ca2+ exchanger in Alzheimer's disease

被引:36
|
作者
Pannaccione, Anna [1 ]
Piccialli, Ilaria [1 ]
Secondo, Agnese [1 ]
Ciccone, Roselia [1 ]
Molinaro, Pasquale [1 ]
Boscia, Francesca [1 ]
Annunziato, Lucio [2 ]
机构
[1] Federico II Univ Naples, Sch Med, Dept Neurosci Reprod & Dent Sci, Div Pharmacol, Via Pansini 5, I-80131 Naples, Italy
[2] IRCSS SDN, Via Gianturco, I-80131 Naples, Italy
关键词
Na+/Ca2+ exchanger; Alzheimer's disease; NCX3; Ionic deregulation; Neuroprotection; AMYLOID-BETA-PEPTIDE; SODIUM-CALCIUM EXCHANGE; D-ASPARTATE RECEPTORS; ENDOPLASMIC-RETICULUM; A-BETA; MOUSE MODEL; MITOCHONDRIAL DYSFUNCTION; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; TRANSGENIC MICE;
D O I
10.1016/j.ceca.2020.102190
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As a pivotal player in regulating sodium (Na+) and calcium (Ca2+) homeostasis and signalling in excitable cells, the Na+/Ca2+ exchanger (NCX) is involved in many neurodegenerative disorders in which an imbalance of intracellular Ca2+ and/or Na+ concentrations occurs, including Alzheimer's disease (AD). Although NCX has been mainly implicated in neuroprotective mechanisms counteracting Ca2+ dysregulation, several studies highlighted its role in the neuronal responses to intracellular Na+ elevation occurring in several pathophysiological conditions. Since the alteration of Na+ and Ca2+ homeostasis significantly contributes to synaptic dysfunction and neuronal loss in AD, it is of crucial importance to analyze the contribution of NCX isoforms in the homeostatic responses at neuronal and synaptic levels. Some studies found that an increase of NCX activity in brains of AD patients was correlated with neuronal survival, while other research groups found that protein levels of two NCX subtypes, NCX2 and NCX3, were modulated in parietal cortex of late stage AD brains. In particular, NCX2 positive synaptic terminals were increased in AD cohort while the number of NCX3 positive terminals were reduced. In addition, NCX1, NCX2 and NCX3 isoforms were up-regulated in those synaptic terminals accumulating amyloid-beta (A beta), the neurotoxic peptide responsible for AD neurodegeneration. More recently, the hyperfunction of a specific NCX subtype, NCX3, has been shown to delay endoplasmic reticulum stress and apoptotic neuronal death in hippocampal neurons exposed to A beta insult. Despite some issues about the functional role of NCX in synaptic failure and neuronal loss require further studies, these findings highlight the putative neuroprotective role of NCX in AD and open new strategies to develop new druggable targets for AD therapy.
引用
收藏
页数:10
相关论文
共 50 条
  • [1] Role of Na+/Ca2+ exchanger in Alzheimer's disease
    Moriguchi, Shigeki
    Kita, Satomi
    Iwamoto, Takahiro
    Fukunaga, Kohji
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2014, 124 : 121P - 121P
  • [2] Topics on the Na+/Ca2+ exchanger:: Pharmacological characterization of Na+/Ca2+ exchanger inhibitors
    Watanabe, Yasuhide
    Koide, Yuuki
    Kimura, Junko
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2006, 102 (01) : 7 - 16
  • [3] Ca2+ regulation of the Na+/Ca2+ exchanger
    Chaptal, Vincent
    Mercado-Besserer, Gabriel
    Ottolia, Michela
    Nicoll, Deborah
    Philipson, Kenneth
    Abramson, Jeff
    FASEB JOURNAL, 2009, 23
  • [4] The mitochondrial Na+/Ca2+ exchanger
    Palty, Raz
    Sekler, Israel
    CELL CALCIUM, 2012, 52 (01) : 9 - 15
  • [5] Inhibitors of Na+/Ca2+ exchanger
    Watanabe, Y
    Iwamoto, T
    Kimura, J
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2005, 97 : 55P - 55P
  • [6] Pharmacology of Na+/Ca2+ exchanger
    Kimura, J
    Watanabe, Y
    Li, LB
    Watano, T
    CELLULAR AND MOLECULAR PHYSIOLOGY OF SODIUM-CALCIUM EXCHANGE, 2002, 976 : 513 - 519
  • [7] Topics on the Na+/Ca2+ exchanger:: Involvement of Na+/Ca2+ exchanger in the vasodilator-induced vasorelaxation
    Nishimura, Junii
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2006, 102 (01) : 27 - 31
  • [8] Forefront of Na+/Ca2+ exchanger studies:: Regulation kinetics of Na+/Ca2+ exchangers
    Matsuoka, S
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2004, 96 (01) : 12 - 14
  • [9] Forefront of Na+/Ca2+ exchanger studies:: Role of Na+/Ca2+ exchanger -: Lessons from knockout mice
    Komuro, I
    Ohtsuka, M
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2004, 96 (01) : 23 - 26
  • [10] Na+/Ca2+ exchanger, learning, and memory
    不详
    NEUROSCIENTIST, 2003, 9 (06): : 427 - 427