Elucidating biological risk factors in suicide: role of protein kinase A.
Elucidating biological risk factors in suicide: role of protein kinase A.
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DOI：
10.1016/j.pnpbp.2010.08.025
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发表时间：
2011-06-01
影响因子：
5.6
通讯作者：
Pandey, Ghanshyam N.
中科院分区：
文献类型：
--
作者：
Dwivedi, Yogesh;Pandey, Ghanshyam N.
自杀是一个重大的公共卫生问题。虽然已经有几项关于自杀行为的研究集中在社会心理和社会文化因素的作用上，但这些因素的预测价值太小，无法在临床上使用。因此，对自杀的生物学角度的研究已经获得了一个据点，似乎提供了一个有前途的方法来确定与自杀行为相关的生物学风险因素。最近的研究表明，突触和结构可塑性的改变是情感疾病和自杀的关键。信号转导分子在这种可塑性事件中起着重要作用。蛋白激酶A（PKA）是腺苷酸环化酶信号转导途径中的关键酶，参与调节基因转录、细胞存活和可塑性。本文就PKA在自杀行为中的作用作一综述。因为压力是自杀的一个重要组成部分，我们还讨论了压力是否会影响PKA，以及这可能与自杀行为。此外，我们还通过描述重要PKA底物的作用（即，Rap1、环腺苷酸反应元件结合蛋白和靶基因脑源性神经营养因子）。这些研究表明，PKA和相关信号分子可能作为自杀的重要神经生物学因素，并可能在这些疾病的靶向特异性治疗干预相关的可能性。
Suicide is a major public health concern. Although there have been several studies of suicidal behavior that focused on the roles of psychosocial and sociocultural factors, these factors are of too little predictive value to be clinically useful. Therefore, research on the biological perspective of suicide has gained a stronghold and appears to provide a promising approach to identify biological risk factors associated with suicidal behavior. Recent studies demonstrate that an alteration in synaptic and structural plasticity is key to affective illnesses and suicide. Signal transduction molecules play an important role in such plastic events. Protein kinase A (PKA) is a crucial enzyme in the adenylyl cyclase signal transduction pathway and is involved in regulating gene transcription, cell survival, and plasticity. In this review, we critically and comprehensively discuss the role of PKA in suicidal behavior. Because stress is an important component of suicide, we also discuss whether stress affects PKA and how this may be associated with suicidal behavior. In addition, we also discuss the functional significance of the findings regarding PKA by describing the role of important PKA substrates (i.e., Rap1, cyclic adenosine monophosphate–response element binding protein, and target gene brain-derived neurotrophic factor). These studies suggest the interesting possibility that PKA and related signaling molecules may serve as important neurobiological factors in suicide and may be relevant in target-specific therapeutic interventions for these disorders.
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