Chair and Department of Neurology, Poznan University of Medical Sciences, Poland.
General Medicine Department, Armadale Health Service, Mount Nasura, Australia.
Neural Plast. 2021 Mar 29;2021:8834645. doi: 10.1155/2021/8834645. eCollection 2021.
Neural plasticity-the ability to alter a neuronal response to environmental stimuli-is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer's disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates including -amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of -synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians' diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.
神经可塑性——即改变神经元对环境刺激反应的能力——是学习和记忆的重要因素。短期突触可塑性和长期突触可塑性，包括长时程增强和长时程抑制，是分子和细胞水平上学习和记忆最典型的模型。这些过程常被神经退行性疾病引起的痴呆所破坏。阿尔茨海默病（AD）占痴呆症病例的 50%。血管性痴呆（VaD）、帕金森病痴呆（PDD）、路易体痴呆（DLB）和额颞叶痴呆（FTD）构成了其余大部分病例。虽然血管病变是 VaD 的主要原因，但神经退行性过程已被确定为许多痴呆疾病的病因。其中主要的过程是病理性蛋白聚集体的沉积，包括 AD 中的β-淀粉样蛋白沉积、AD 和 FTD 中的神经原纤维缠结形成，以及由β-突触核蛋白聚集组成的 DLB 和 PDD 中的路易体积累。痴呆的主要症状是认知能力下降、记忆力和学习能力受损。尽管如此，由于临床症状重叠和皮质病变部位多样，神经退行性疾病的准确诊断仍可能具有挑战性。然而，新的神经影像学和分子生物标志物提高了临床医生在痴呆背景下的诊断能力，并可能导致更有效的治疗方法的发展。遗传和环境因素都可能导致病理性蛋白的聚集和细胞因子水平的改变，从而引发促炎免疫表型的形成。这种病理变化的级联反应为神经可塑性障碍和痴呆的发展提供了有利条件。目前正在临床试验中的可用药物治疗和疾病修饰疗法可能会调节突触可塑性，减轻神经病理学变化对认知功能、记忆和学习的影响。本文从病理生理学和临床角度综述了常见神经退行性疾病中的神经可塑性变化，并强调了疾病修饰疗法的潜在分子靶点。
