TY - JOUR
T1 - Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer’s and Parkinson’s Disease
AU - Gutierrez, Berenice A.
AU - Limon, Agenor
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/7
Y1 - 2022/7
N2 - Neurodegenerative diseases are the result of progressive dysfunction of the neuronal activity and subsequent neuronal death. Currently, the most prevalent neurodegenerative diseases are by far Alzheimer’s (AD) and Parkinson’s (PD) disease, affecting millions of people worldwide. Although amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks for AD and Lewy bodies (LB) are the hallmark for PD, current evidence strongly suggests that oligomers seeding the neuropathological hallmarks are more toxic and disease-relevant in both pathologies. The presence of small soluble oligomers is the common bond between AD and PD: amyloid β oligomers (AβOs) and Tau oligomers (TauOs) in AD and α-synuclein oligomers (αSynOs) in PD. Such oligomers appear to be particularly increased during the early pathological stages, targeting synapses at vulnerable brain regions leading to synaptic plasticity disruption, synapse loss, inflammation, excitation to inhibition imbalance and cognitive impairment. Absence of TauOs at synapses in individuals with strong AD disease pathology but preserved cognition suggests that mechanisms of resilience may be dependent on the interactions between soluble oligomers and their synaptic targets. In this review, we will discuss the current knowledge about the interactions between soluble oligomers and synaptic dysfunction in patients diagnosed with AD and PD, how it affects excitatory and inhibitory synaptic transmission, and the potential mechanisms of synaptic resilience in humans.
AB - Neurodegenerative diseases are the result of progressive dysfunction of the neuronal activity and subsequent neuronal death. Currently, the most prevalent neurodegenerative diseases are by far Alzheimer’s (AD) and Parkinson’s (PD) disease, affecting millions of people worldwide. Although amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks for AD and Lewy bodies (LB) are the hallmark for PD, current evidence strongly suggests that oligomers seeding the neuropathological hallmarks are more toxic and disease-relevant in both pathologies. The presence of small soluble oligomers is the common bond between AD and PD: amyloid β oligomers (AβOs) and Tau oligomers (TauOs) in AD and α-synuclein oligomers (αSynOs) in PD. Such oligomers appear to be particularly increased during the early pathological stages, targeting synapses at vulnerable brain regions leading to synaptic plasticity disruption, synapse loss, inflammation, excitation to inhibition imbalance and cognitive impairment. Absence of TauOs at synapses in individuals with strong AD disease pathology but preserved cognition suggests that mechanisms of resilience may be dependent on the interactions between soluble oligomers and their synaptic targets. In this review, we will discuss the current knowledge about the interactions between soluble oligomers and synaptic dysfunction in patients diagnosed with AD and PD, how it affects excitatory and inhibitory synaptic transmission, and the potential mechanisms of synaptic resilience in humans.
KW - E/I balance
KW - neurodegenerative diseases
KW - oligomers
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U2 - 10.3390/biomedicines10071743
DO - 10.3390/biomedicines10071743
M3 - Review article
C2 - 35885050
AN - SCOPUS:85136435671
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 7
M1 - 1743
ER -