2021
DOI: 10.3389/fncel.2021.626128
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Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson’s Disease

Abstract: Parkinson’s disease (PD) is a progressive neurodegenerative disease that impairs movement as well as causing multiple other symptoms such as autonomic dysfunction, rapid eye movement (REM) sleep behavior disorder, hyposmia, and cognitive changes. Loss of dopamine neurons in the substantia nigra pars compacta (SNc) and loss of dopamine terminals in the striatum contribute to characteristic motor features. Although therapies ease the symptoms of PD, there are no treatments to slow its progression. Accumulating e… Show more

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Cited by 54 publications
(35 citation statements)
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“…LRRK2 also plays a major role in membrane trafficking [ 25 , 69 ]. Defects in trafficking and targeting of α-synuclein to the correct membrane compartment within the neuron may influence its propensity to aggregate [ 70 ]. α-Synuclein primarily localizes to the presynaptic terminal [ 16 , 71 74 ] where it interacts with the SNARE complex to reduce synaptic vesicle exocytosis [ 13 , 14 ].…”
Section: Discussionmentioning
confidence: 99%
“…LRRK2 also plays a major role in membrane trafficking [ 25 , 69 ]. Defects in trafficking and targeting of α-synuclein to the correct membrane compartment within the neuron may influence its propensity to aggregate [ 70 ]. α-Synuclein primarily localizes to the presynaptic terminal [ 16 , 71 74 ] where it interacts with the SNARE complex to reduce synaptic vesicle exocytosis [ 13 , 14 ].…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, synapse loss has been shown to occur early in the neurodegenerative process, for example in the retina of glaucoma models and patients, or in the brain of AD or PD models and patients (Selkoe, 2002;Della Santina et al, 2013;Purro et al, 2014;Bellucci et al, 2016;Subramanian and Tremblay, 2021). More specifically, a decrease in synaptic volume in of pre-and post-synapses has been reported in the striatum of PD patients (Bellucci et al, 2016;Reeve et al, 2018;Gcwensa et al, 2021). Of note, an age-related decrease of postsynaptic retinal proteins was also observed in the plexiform layers of Octodon degus, the only rodent with naturally occurring AD (Chang et al, 2020).…”
Section: Discussionmentioning
confidence: 99%
“…It has recently been recognized that presynaptic alterations play important roles in neurodegenerative diseases and that these changes occur in the early, prodromal phase of PD, preceding DA neuron loss (Gcwensa et al, 2021). Given that excessive glutamate release can lead to neurotoxicity and neuronal death (Wang et al, 2020), it is possible that an altered LRRK2 function in glutamatergic synapses onto SNc‐DA neurons contributes to G2019S‐linked PD pathology.…”
Section: Introductionmentioning
confidence: 99%