Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?
Nat Rev Neurosci. 2021-12-14; :
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Blesa J(#)(1)(2), Foffani G(#)(1)(2)(3), Dehay B(4), Bezard E(4), Obeso JA(5)(6)(7).
(1)HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.
(2)Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain.
(3)Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
(4)Univ. Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
(5)HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain. .
(6)Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. .
(7)University CEU-San Pablo, Madrid, Spain. .
For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD.
© 2021. Springer Nature Limited.