Blanchette Rockefeller Neurosciences Institute, Morgantown, West Virginia, USA.
Prog Mol Biol Transl Sci. 2014;122:31-59. doi: 10.1016/B978-0-12-420170-5.00002-7.
The protein kinase C (PKC) isoforms, which play an essential role in transmembrane signal conduction, can be viewed as a family of "memory kinases." Evidence is emerging that they are critically involved in memory acquisition and maintenance, in addition to their involvement in other functions of cells. Deficits in PKC signal cascades in neurons are one of the earliest abnormalities in the brains of patients suffering from Alzheimer's disease. Their dysfunction is also involved in several other types of memory impairments, including those related to emotion, mental retardation, brain injury, and vascular dementia/ischemic stroke. Inhibition of PKC activity leads to a reduced capacity of many types of learning and memory, but may have therapeutic values in treating substance abuse or aversive memories. PKC activators, on the other hand, have been shown to possess memory-enhancing and antidementia actions. PKC pharmacology may, therefore, represent an attractive area for developing effective cognitive drugs for the treatment of many types of memory disorders and dementias.
蛋白激酶 C(PKC)同工型在跨膜信号转导中发挥着重要作用,可被视为“记忆激酶”家族的一员。有证据表明,除了参与细胞的其他功能外,它们还与记忆的获得和维持密切相关。在患有阿尔茨海默病的患者的大脑中,神经元中 PKC 信号级联的缺陷是最早的异常之一。它们的功能障碍也与其他几种类型的记忆障碍有关,包括与情绪、智力迟钝、脑损伤和血管性痴呆/缺血性中风有关的记忆障碍。抑制 PKC 活性会导致多种类型的学习和记忆能力下降,但在治疗药物滥用或厌恶记忆方面可能具有治疗价值。另一方面,PKC 激活剂已被证明具有增强记忆和抗痴呆作用。因此,PKC 药理学可能是开发治疗多种类型记忆障碍和痴呆症的有效认知药物的有吸引力的领域。