Parkinson's disease outside the brain: targeting the autonomic nervous system.

Published on Oct 1, 2021in Lancet Neurology44.182
· DOI :10.1016/S1474-4422(21)00219-2
Yehonatan Sharabi25
Estimated H-index: 25
(TAU: Tel Aviv University),
Gad Vatine14
Estimated H-index: 14
(BGU: Ben-Gurion University of the Negev),
Avraham Ashkenazi17
Estimated H-index: 17
(TAU: Tel Aviv University)
Patients with Parkinson's disease present with signs and symptoms of dysregulation of the peripheral autonomic nervous system that can even precede motor deficits. This dysregulation might reflect early pathology and therefore could be targeted for the development of prodromal or diagnostic biomarkers. Only a few objective clinical tests assess disease progression and are used to evaluate the entire spectrum of autonomic dysregulation in patients with Parkinson's disease. However, results from epidemiological studies and findings from new animal models suggest that the dysfunctional autonomic nervous system is a probable route by which Parkinson's disease pathology can spread both to and from the CNS. The autonomic innervation of the gut, heart, and skin is affected by α-synuclein pathology in the early stages of the disease and might initiate α-synuclein spread via the autonomic connectome to the CNS. The development of easy-to-use and reliable clinical tests of autonomic nervous system function seems crucial for early diagnosis, and for developing strategies to stop or prevent neurodegeneration in Parkinson's disease.
#1Christopher E J Doppler (Forschungszentrum Jülich)H-Index: 2
#2Julia A M Smit (University of Cologne)H-Index: 1
Last. Michael Sommerauer (Forschungszentrum Jülich)H-Index: 8
view all 13 authors...
Study objectives Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients. Methods We analysed 27 PD patients and 13 healthy control (HC) subjects w...
#1Conor Fearon (Toronto Western Hospital)H-Index: 3
#2Anthony E. Lang (Toronto Western Hospital)H-Index: 168
Last. Alberto J. Espay (UC: University of Cincinnati)H-Index: 59
view all 3 authors...
#1Anna Masato (UNIPD: University of Padua)H-Index: 2
#2Michele Sandre (UNIPD: University of Padua)H-Index: 7
Last. Luigi Bubacco (UNIPD: University of Padua)H-Index: 53
view all 4 authors...
Parkinson's disease (PD) is a clinically heterogeneous disorder with a multi-factorial pathology. Various molecular mechanisms are involved in the pathogenesis of PD, converging to oxidative stress and proteinopathy. The accumulation of reactive aldehydes (i.e., the dopamine metabolite DOPAL, lipid-peroxidation products, and advanced glycation end-products) has been reported in PD patients' brains. Aldehydes easily react with primary amines such as lysine residues, which are involved in several ...
Abstract The catecholamine-containing brainstem nuclei locus coeruleus (LC) and ventral tegmental area (VTA) are critically involved in stress responses. Alterations of catecholamine systems during chronic stress may contribute to neurodegeneration, including cognitive decline. Stress-related catecholamine alterations, while contributing to anxiety and depression, might accelerate neuronal degeneration by increasing the formation of toxic dopamine and norepinephrine by-products. These, in turn, ...
#1Jie Sun (HMU: Harbin Medical University)H-Index: 1
#2Chao He (HMU: Harbin Medical University)H-Index: 1
Last. Bai-Yan Li (HMU: Harbin Medical University)H-Index: 16
view all 15 authors...
Aim To understand why autonomic failures, a common non-motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders. Methods Vagal application of DOPAL (3,4-dihydroxyphenylacetaldehyde) to simulate PD-like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time-dependent alternation of α-synuclein aggregation and the ultrastructure changes in the heart and nodose ...
#1Polyxeni Nikolakopoulou (KI: Karolinska Institutet)H-Index: 6
#2Rossana Rauti (TAU: Tel Aviv University)H-Index: 11
Last. Anna Herland (KI: Karolinska Institutet)H-Index: 31
view all 6 authors...
The complexity of the human brain poses a substantial challenge for the development of models of the CNS. Current animal models lack many essential human characteristics (in addition to raising operational challenges and ethical concerns), and conventional in vitro models, in turn, are limited in their capacity to provide information regarding many functional and systemic responses. Indeed, these challenges may underlie the notoriously low success rates of CNS drug development efforts. During th...
#1Senthil T. Kumar (MIND Institute)H-Index: 12
#2Somanath Jagannath (MIND Institute)H-Index: 3
Last. Hilal A. Lashuel (MIND Institute)H-Index: 79
view all 6 authors...
Increasing evidence suggests that alpha-synuclein (α-syn) oligomers are obligate intermediates in the pathway involved in α-syn fibrillization and Lewy body (LB) formation, and may also accumulate within LBs in Parkinson's disease (PD) and other synucleinopathies. Therefore, the development of tools and methods to detect and quantify α-syn oligomers has become increasingly crucial for mechanistic studies to understand their role in PD, and to develop new diagnostic methods and therapies for PD a...
#1Jian-Yong Wang (WMU: Wenzhou Medical College)H-Index: 6
#2Meng‐Yan Wang (WMU: Wenzhou Medical College)H-Index: 2
Last. Jian-Hong Zhu (WMU: Wenzhou Medical College)H-Index: 18
view all 8 authors...
Introduction: Autonomic dysfunction is a common and disabling non-motor symptom of Parkinson’s disease (PD). We aimed to understand autonomic dysfunction in PD motor subtypes, the pattern of sympathetic skin response (SSR) to motor asymmetry, and the association of SSR with autonomic and motor dysfunctions. Methods: A total of 101 PD patients of Han Chinese were included. Unified PD rating scale (UPDRS), scales for outcomes in PD-autonomic symptoms (SCOPA-AUT), orthostatic hypotension, and SSR w...
The aggregation of α-synuclein (aSyn) is believed to be mechanistically linked to the degeneration of dopamine (DA)-producing neurons in Parkinson's disease (PD). In this respect, one crucial question that yet remains unsolved is whether aSyn aggregation is associated with either a gain- or loss-of-function of the protein in neuronal cells. Herein, we investigated the effect of monomeric versus fibrillar aSyn on mesencephalic dopaminergic neurons in primary cultures challenged with the neurotoxi...
#1Koichi Wakabayashi (Hirosaki University)H-Index: 80
In Parkinson's disease (PD), neuronal alpha-synuclein aggregates are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, submandibular gland, enteric nervous system, cardiac and pelvic plexuses, adrenal medulla, and skin. Thus, PD is a progressive multiorgan disease clinically associated with various motor and nonmotor symptoms. The earliest PD-related lesions appear to develop in the olfactory bulb, dorsal vagal nucleus, and possibly also the periph...
Cited By1
#1Alessandra Fanciulli (Innsbruck Medical University)H-Index: 19
#2Gregor K. Wenning (Innsbruck Medical University)H-Index: 112
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.