Research Progress on molecular mechanism of olfactory dysfunction in Parkinson's disease

Upload time:2017-02-23 Browse:

Author: Chen Zejie, Zhang Wei, Wang Ruidan
Abstract: Parkinson's disease is a neurodegenerative diseases common in the elderly in recent years, the non motor symptoms are more and more attention, the olfactory disorder with high incidence rate, appeared in the early course of the disease, it has important significance in early diagnosis and differential diagnosis of disease. The brain dopaminergic system, acetylcholine levels and 5- serotonin levels, abnormal olfactory cortex of alpha synuclein and abnormal deposition of Tau protein, increased microglia activation in the olfactory bulb, inflammatory reaction level, and many other factors may be involved in olfactory dysfunction of Parkinson's disease. In this paper, we reviewed the recent advances in the study of molecular mechanisms of olfactory dysfunction in patients with Parkinson's disease in terms of neurobiological mechanisms, neuropathological mechanisms, inflammatory response mechanisms and other factors.
Key words: Parkinson's disease; olfactory disorders; motor symptoms; non motor symptoms; neuropathological proteins; neurotransmitters
CLC number: R742.5 document code: A article number: 1006-2963 (2016)
Disease Parkinson (Parkinson) is a common neurodegenerative disease in the elderly, with the acceleration of the aging process, the incidence and prevalence of PD are increasing rapidly in PD. For a long time, PD is considered as a kind of tremor, rigidity, bradykinesia and posture gait and abnormal motor symptoms as the main clinical features of movement disorders, the neuropathological sign is the substantia nigra pars compacta dopamine (dopamine, DA) neurons degeneration, loss of striatal DA levels were significantly reduced and Louis body formation in the residual neurons (Lewy bodies, LB). Until Braak [1] proposed neuropathological hypothesis which makes people realize, PD were found in patients with non motor symptoms, such as olfactory dysfunction (olfactory dysfunction), cognitive disorders, sleep disorders, autonomic dysfunction and mood disorders, significantly affect the quality of life of patients.
The incidence of olfactory dysfunction in patients with PD is as high as 45% ~ 96.7%[2], according to the Braak hypothesis, olfactory dysfunction may be the first clinical symptoms of PD patients, and run through the process of disease development. In clinical practice, there is to improve the PD diagnosis of olfactory disorder an index of sensitivity and specificity, but also has important significance in the differential diagnosis of PD, therefore, most scholars tend to think that olfactory dysfunction can be used as a clinical index of PD early diagnosis and prognostic evaluation of A. However, the current treatment of PD drugs, such as levodopa, DA receptor agonists and anticholinergic drugs, and so on, the efficacy of olfactory dysfunction. With the emergence of various technical olfactory detection methods and molecular imaging progress, PD has received great attention of olfactory dysfunction, clinical features, pathogenesis, diagnosis and treatment has become a hot research in recent years.
In recent years, the development of neuropathology, especially the development of immunohistochemical labeling technique, makes people have a deeper understanding of the neuropathological features and pathogenesis of PD. At present, PD is considered to be a result of aging, genetic susceptibility and environmental factors, and its specific pathogenesis is not clear. Research shows that PD may induce mitochondrial dysfunction, oxidative stress, the ubiquitin proteasome system dysfunction, immune disorders, neuro immune inflammatory reaction, the toxicity of excitatory amino acids and cells apoptosis. No matter what kind of mechanism, it may eventually lead to abnormal pathological protein deposition, cell dysfunction and the balance of neurotransmitters, resulting in a series of motor symptoms and non motor symptoms. However, at present, the research on the mechanism of PD is still in the exploratory stage. In this paper, the research progress on the molecular mechanism of olfactory dysfunction in PD is reviewed.
1 neurobiological mechanisms
Recent studies have found that the change of PD occurs not only with the level of DA in brain, at the same time there are many neurotransmitters involved, such as acetylcholine (acetylcholine, Ach), norepinephrine (norepinephrine, NE) and 5- (5-hydroxytryptamine, serotonin, 5-HT HT) etc.. PD may be involved in the development of olfactory dysfunction by one or several neurotransmitters, at the same time, the interaction between different neurotransmitters.
1.1 DA PD were substantia nigra and the ventral tegmental area containing nerve melanin DA neurons degeneration, and the ventral tegmental area is the main source of project to the olfactory bulb and other limbic system DA fiber at the same time, this degeneration process is independent without nerve melanin therefore, [3] cells, some scholars speculate that there is a certain relation between the abnormal PD and DA olfactory system can.
It was found that there was an independent correlation between PD olfactory dysfunction and the DA level of synaptic gap, but the olfactory test score was not related to DA saturation ([4]). However, for PD patients with autopsy found that increased expression of olfactory bulb juxtaglomerular cell region of tyrosine hydroxylase DA neurons with the increase of the number of no DA levels in the olfactory bulb decreased [5], this phenomenon in the mutation of alpha synuclein (alpha -synuclein) transgenic mice exposed to [9] and 1- methyl -4- phenyl -1,2,3,6- four hydrogen pyridine (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) confirmed by olfactory pathway in wild-type mice and monkeys in Ganges RIver.
DA transporter (dopamine transporter, DAT) in DA neurons through presynaptic membrane, synaptic reuptake of DA to limit (dopamine receptor, DA receptor DR) activation, suspend the communication between nerve cells. Swanson et al. Study of PD olfactory dysfunction and brain by DAT imaging