The Expression of α-, β-, and γ-Synucleins in Olfactory Mucosa from Patients with and without Neurodegenerative Diseases

Duda, John E.; Shah, Usman; Arnold, Steven E.; Lee, Virginia M.‐Y.; Trojanowski, John Q.

doi:10.1006/exnr.1999.7228

Cited by 123 publications

(79 citation statements)

References 40 publications

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“…Furthermore, a-SYN expression was detected in the olfactory mucosa with no difference between controls and patients with neurodegenerative diseases. Therefore, it is uncertain if the accumulation of a-SYN contributes to the common occurrence of olfactory dysfunction in AD, PD, MSA, and other neurodegenerative disorders (Duda et al 1999). Up to now, no published data have revealed if a-SYN is involved in the development of the olfactory mucosa.…”

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confidence: 98%

Expression and Subcellular Location of Alpha-Synuclein During Mouse-Embryonic Development

et al. 2009

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Alpha-synuclein (alpha-SYN) is one of the major components of intracellular fibrillary aggregates in the brains of a subset of neurodegenerative disorders. Although alpha-SYN expression has been found in developing mouse brain, a detailed distribution during mouse-embryonic development has not been made. Here we describe the expression pattern of alpha-SYN during the development of mice from E9.5 to P0 by immunohistochemistry (IHC). As a result, alpha-SYN was detected as early as E9.5. During the embryonic stages, alpha-SYN was dynamically expressed in several regions of the brain. In the neocortex, expression was detected in the marginal zone (MZ) in the early stages and was later condensed in the MZ and in the subplate (SP); in the cerebellum, expression was initially detected in the deep cerebellar nuclei (DCN) and was later condensed in the Purkinje cells. These spatio-temporal expression patterns matched the neuronal migratory pathways and the formation of the synapse connections. Additionally, alpha-SYN was detected in the sensory systems, including the nasal mucosa, the optic cup, the sensory ganglia, and their dominating nerve fibers. Furthermore, the nuclear location of alpha-SYN protein was found in developing neurons in the early stages, and later it was mostly found in the non-nuclear compartments. This finding was further confirmed by Western blot analysis. These results suggest that alpha-SYN may be involved not only in the migration of neurons and in the synaptogenesis of the central nervous system (CNS) but also in the establishment of the sensory systems. The nuclear location of alpha-SYN may hint at an important function in these events.

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confidence: 98%

Expression and Subcellular Location of Alpha-Synuclein During Mouse-Embryonic Development

et al. 2009

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“…6 The same is true for the expression of a-synuclein which contributes little to the diagnosis of PD. 6,7 Goals of this study were therefore as follows: (1) to identify possible specific histological/histochemical changes of the olfactory epithelium in patients with PD, (2) to find morphological correlates of olfactory function, and (3) to compare biopsy material from PD patients with that from patients with olfactory dysfunction due to other reasons, e.g., congenital anosmia or postinfectious olfactory loss.…”

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Biopsies of olfactory epithelium in patients with Parkinson's disease

Witt

Bormann

Gudziol³

et al. 2009

Movement Disorders

138

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Parkinson's disease (PD) is a neurodegenerative disorder involving several neuronal systems. Impaired olfactory function may constitute one of the earliest symptoms of PD. However, it is still unclear to what degree changes of the olfactory epithelium may contribute to dysosmia and if these changes are different from those of other hyposmic or anosmic patients. This study aimed to investigate the hypothesis that olfactory loss in PD is a consequence of specific PD-related damage of olfactory epithelium. Biopsies of 7 patients diagnosed with PD were taken. Six patients with PD were hyposmic, one anosmic. As non-PD controls served 9 patients with hyposmia, 9 with anosmia, and 7 normosmic individuals. Further, nasal mucosa of 4 postmortem individuals was investigated. Immunohistochemical examinations were performed with antibodies against olfactory marker protein (OMP), protein gene product 9.5 (PGP 9.5), beta-tubulin, (BT), proliferation-associated antigen (Ki 67), the stem cell marker nestin, cytokeratin, p75NGFr, and alpha-synuclein. Most of the biopsy specimens exhibited irregular areas of olfactory-like, dysplastic epithelium positive for either PGP 9.5 or BT, but negative for OMP. No major histochemical differences in either the expression or distribution of these proteins were observed in the olfactory epithelium of patients with PD compared with controls. Reverse transcription PCR (RT-PCR) data indicated mRNA for OMP in almost all subjects, independently of their olfactory performance. These data support the idea that olfactory loss in Parkinson's disease is not a consequence of damage to the olfactory epithelium but rather results from distinct central-nervous abnormalities.

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“…Tau-containing dystrophic neurites were present not only in AD, but also in other neurodegenerative diseases, as well as in normal aging; only fetal and neonatal cases were found to not possess them [10]. Recently, the pathology of the olfactory epithelium was studied in detail by Arnold et al [14] in a large number of neurites in the olfactory epithelium [15]. TDP-43-containing inclusions were not found.…”

Section: Hyperphosphorylated Tau Lamentsmentioning

confidence: 99%

The olfactory system in Alzheimer’s disease: Pathology, pathophysiology and pathway for therapy

Kovács

2013

Translational Neuroscience

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Olfaction is frequently mentioned as a "neglected sense", although the olfactory system has several interesting and unique anatomical and physiological features. Olfactory involvement is present in several degenerative disorders, especially in Alzheimer's disease (AD). The peripheral and central parts of the olfactory system are damaged even in the early stages of AD, manifesting in profound olfactory deficits. Besides the early pathology, the olfactory system may be involved in the pathogenesis of AD by providing a route of entry for pathological agents still unknown. In contrast to this olfactory vector hypothesis, the olfactory system can be used to deliver therapeutic agents in AD, such as nerve growth factor and insulin, by decreasing the side-effects of the therapy or providing a non-invasive method of delivery.

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The Expression of α-, β-, and γ-Synucleins in Olfactory Mucosa from Patients with and without Neurodegenerative Diseases

Cited by 123 publications

References 40 publications

Expression and Subcellular Location of Alpha-Synuclein During Mouse-Embryonic Development

Expression and Subcellular Location of Alpha-Synuclein During Mouse-Embryonic Development

Biopsies of olfactory epithelium in patients with Parkinson's disease

The olfactory system in Alzheimer’s disease: Pathology, pathophysiology and pathway for therapy

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