Dibattista Michele, Pifferi Simone, Menini Anna, Reisert Johannes
Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari A. Moro, Bari, Italy.
Neurobiology Group, SISSA, Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
Front Neurosci. 2020 May 19;14:440. doi: 10.3389/fnins.2020.00440. eCollection 2020.
The sense of smell has been shown to deteriorate in patients with some neurodegenerative disorders. In Parkinson's disease (PD) and Alzheimer's disease (AD), decreased ability to smell is associated with early disease stages. Thus, olfactory neurons in the nose and olfactory bulb (OB) may provide a window into brain physiology and pathophysiology to address the pathogenesis of neurodegenerative diseases. Because nasal olfactory receptor neurons regenerate throughout life, the olfactory system offers a broad variety of cellular mechanisms that could be altered in AD, including odorant receptor expression, neurogenesis and neurodegeneration in the olfactory epithelium, axonal targeting to the OB, and synaptogenesis and neurogenesis in the OB. This review focuses on pathophysiological changes in the periphery of the olfactory system during the progression of AD in mice, highlighting how the olfactory epithelium and the OB are particularly sensitive to changes in proteins and enzymes involved in AD pathogenesis. Evidence reviewed here in the context of the emergence of other typical pathological changes in AD suggests that olfactory impairments could be used to understand the molecular mechanisms involved in the early phases of the pathology.
嗅觉已被证明在一些神经退行性疾病患者中会恶化。在帕金森病（PD）和阿尔茨海默病（AD）中，嗅觉能力下降与疾病早期阶段相关。因此，鼻腔中的嗅觉神经元和嗅球（OB）可能为了解大脑生理和病理生理提供一个窗口，以探讨神经退行性疾病的发病机制。由于鼻腔嗅觉受体神经元终生再生，嗅觉系统提供了多种可能在AD中发生改变的细胞机制，包括气味受体表达、嗅觉上皮中的神经发生和神经变性、轴突靶向至OB以及OB中的突触形成和神经发生。本综述聚焦于小鼠AD进展过程中嗅觉系统外周的病理生理变化，强调嗅觉上皮和OB如何对AD发病机制中涉及的蛋白质和酶的变化特别敏感。在AD中其他典型病理变化出现的背景下，这里所综述的证据表明嗅觉障碍可用于理解病理早期阶段所涉及的分子机制。
