TY - JOUR
T1 - The End Is the Beginning
T2 - Parkinson's Disease in the Light of Brain Imaging
AU - Bellucci, Arianna
AU - Antonini, Angelo
AU - Pizzi, Marina
AU - Spano, PierFranco
PY - 2017
Y1 - 2017
N2 - Parkinson's disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healing.
AB - Parkinson's disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healing.
U2 - 10.3389/fnagi.2017.00330
DO - 10.3389/fnagi.2017.00330
M3 - Article
C2 - 29066967
VL - 9
SP - 330
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
SN - 1663-4365
ER -