From understanding synaptic plasticity to the development of cognitive enhancers

被引:17
作者
Cheung, Zelda H.
Ip, Nancy Y. [1 ]
机构
[1] Hong Kong Univ Sci & Technol, Div Life Sci, State Key Lab Mol Neurosci, Kowloon, Hong Kong, Peoples R China
关键词
Alzheimer's disease; BDNF; dendritic spines; depression; synaptic plasticity; DENDRITIC SPINE LOSS; NMDA RECEPTOR TRAFFICKING; ALZHEIMERS-DISEASE; STRUCTURAL PLASTICITY; NEUROTROPHIC FACTOR; AMYLOID-BETA; MOLECULAR-MECHANISMS; PROTEIN-SYNTHESIS; MESSENGER-RNAS; STRESS;
D O I
10.1017/S1461145710001537
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Accumulating evidence reveals that synaptic dysfunction precedes neuronal loss in neurodegenerative diseases such as Alzheimer's disease. Intriguingly, synaptic abnormality is also implicated in a myriad of psychiatric disorders including depression. In particular, alterations in spine density and morphology have been associated with aberrant synaptic activity in these diseased brains. Understanding the molecular mechanisms underlying the regulation of spine morphogenesis, synaptic function and plasticity under physiological and pathological conditions will therefore provide critical insights for the development of potential therapeutic agents against these diseases. Here we summarize existing knowledge on some of the molecular players in synaptic plasticity, and highlight how these findings from basic neuro-scientific research aid in the identification of novel drug leads for the development of therapeutics.
引用
收藏
页码:1247 / 1256
页数:10
相关论文
共 73 条
  • [31] The molecular neurobiology of depression
    Krishnan, Vaishnav
    Nestler, Eric J.
    [J]. NATURE, 2008, 455 (7215) : 894 - 902
  • [32] Aβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61
    Kurup, Pradeep
    Zhang, Yongfang
    Xu, Jian
    Venkitaramani, Deepa V.
    Haroutunian, Vahram
    Greengard, Paul
    Nairn, Angus C.
    Lombroso, Paul J.
    [J]. JOURNAL OF NEUROSCIENCE, 2010, 30 (17) : 5948 - 5957
  • [33] Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease
    Lacor, Pascale N.
    Buniel, Maria C.
    Furlow, Paul W.
    Clemente, Antonio Sanz
    Velasco, Pauline T.
    Wood, Margaret
    Viola, Kirsten L.
    Klein, William L.
    [J]. JOURNAL OF NEUROSCIENCE, 2007, 27 (04) : 796 - 807
  • [34] Recent advances in understanding the roles of Cdk5 in synaptic plasticity
    Lai, Kwok-On
    Ip, Nancy Y.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (08): : 741 - 745
  • [35] NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
    Lau, C. Geoffrey
    Zukin, R. Suzanne
    [J]. NATURE REVIEWS NEUROSCIENCE, 2007, 8 (06) : 413 - 426
  • [36] Regulation of NMDA receptors by cyclin-dependent kinase-5
    Li, BS
    Sun, MK
    Zhang, L
    Takahashi, S
    Ma, W
    Vinade, L
    Kulkarni, AB
    Brady, RO
    Pant, HC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (22) : 12742 - 12747
  • [37] Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond
    Lipton, SA
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (02) : 160 - 170
  • [38] Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting
    Liston, Conor
    Miller, Melinda M.
    Goldwater, Deena S.
    Radley, Jason J.
    Rocher, Anne B.
    Hof, Patrick R.
    Morrison, John H.
    McEwen, Bruce S.
    [J]. JOURNAL OF NEUROSCIENCE, 2006, 26 (30) : 7870 - 7874
  • [39] The yin and yang of neurotrophin action
    Lu, B
    Pang, PT
    Woo, NH
    [J]. NATURE REVIEWS NEUROSCIENCE, 2005, 6 (08) : 603 - 614
  • [40] NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus
    Maekawa, Motoko
    Namba, Takashi
    Suzuki, Eri
    Yuasa, Shigeki
    Kohsaka, Shinichi
    Uchino, Shigeo
    [J]. NEUROSCIENCE RESEARCH, 2009, 63 (04) : 259 - 266