The neurobiology of dysautonomia in Parkinson’s disease

Abstract

Neurodegenerative diseases (NDs) include a large variety of disorders that affects specific areas of the central
nervous system, leading to psychiatric and movement pathologies. A common feature that characterizes these
disorders is the neuronal formation and accumulation of misfolded protein aggregates that lead to cell death. In
particular, different proteinaceous aggregates accumulate to trigger a variety of clinical manifestations: prion
protein (PrPSc) in prion diseases, β-amyloid (Aβ) in Alzheimer’s disease (AD), α-synuclein in Parkinson’s disease
(PD), huntingtin in Huntington’s disease (HD), superoxide dismutase and TDP-43 in amyotrophic lateral sclerosis
(ALS), tau in tauopathies. Non-motor alterations also occur in several viscera, in particular the gastrointestinal
tract. These often precede the onset of motor symptoms by several years. For this reason, dysautonomic changes
can be predictive of NDs and their correct recognition is being assuming a remarkable importance. This peculiar
feature led more and more to the concept that neurodegeneration may initiate in the periphery and propagate retrogradely
towards the central nervous system in a prion-like manner. In recent years, a particular attention was
dedicated to the clinical assessment of autonomic disorders in patients affected by NDs. In this respect, experimental
animal models have been developed to understand the neurobiology underlying these effects as well as to
investigate autonomic changes in peripheral organs. This review summarizes experimental studies that have been
carried out to understand autonomic symptoms in NDs, with the purpose to provide appropriate tools for comprehensive
and integrated studies.