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      α-Synuclein in the olfactory system in Parkinson's disease: role of neural connections on spreading pathology.

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          Abstract

          Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, resting tremor, and postural instability. Neuropathologically, intracellular aggregates of α-synuclein in Lewy bodies and Lewy neurites appear in particular brain areas according to a sequence of stages. Clinical diagnosis is usually established when motor symptoms are evident (corresponding to Braak stage III or later), years or even decades after onset of the disease. Research at early stages is therefore essential to understand the etiology of PD and improve treatment. Although classically considered as a motor disease, non-motor symptoms have recently gained interest. Olfactory deficits are among the earliest non-motor features of PD. Interestingly, α-synuclein deposits are present in the olfactory bulb and anterior olfactory nucleus at Braak stage I. Several lines of evidence have led to proposals that PD pathology spreads by a prion-like mechanism via the olfactory and vagal systems to the substantia nigra. In this context, current data on the temporal appearance of α-synuclein aggregates in the olfactory system of both humans and transgenic mice are of particular relevance. In addition to the proposed retrograde nigral involvement via brainstem nuclei, olfactory pathways could potentially reach the substantia nigra, and the possibility of centrifugal progression warrants investigation. This review analyzes the involvement of α-synuclein in different elements of the olfactory system, in both humans and transgenic models, from the hodological perspective of possible anterograde and/or retrograde progression of this proteinopathy within the olfactory system and beyond-to the substantia nigra and the remainder of the central and peripheral nervous systems.

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          Author and article information

          Journal
          Brain Struct Funct
          Brain structure & function
          Springer Nature
          1863-2661
          1863-2653
          Sep 2014
          : 219
          : 5
          Affiliations
          [1 ] Laboratorio de Neuroplasticidad y Neurodegeneración, Departamento de Ciencias Médicas, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avda. de Moledores s/n, 13071, Ciudad Real, Spain.
          Article
          10.1007/s00429-013-0651-2
          24135772
          3e098e9f-888d-4dbe-a707-990f78ae96c6
          History

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