Abstract
Synapses are sites of cell-cell contacts that transmit electrical or chemical signals in the brain. Dendritic spines are protrusions on dendritic shaft where excitatory synapses are located. Synapses and dendritic spines are dynamic structures whose plasticity is thought to underlie learning and memory. No wonder neurobiologists are intensively studying mechanisms governing the structural and functional plasticity of synapses and dendritic spines in an effort to understand and eventually treat neurological disorders manifesting learning and memory deficits. One of the best-studied brain disorders that prominently feature synaptic and dendritic spine pathology is Alzheimer's disease (AD). Recent studies have revealed molecular mechanisms underlying the synapse and spine pathology in AD, including a role for mislocalized tau in the postsynaptic compartment. Synaptic and dendritic spine pathology is also observed in other neurodegenerative disease. It is possible that some common pathogenic mechanisms may underlie the synaptic and dendritic spine pathology in neurodegenerative diseases.
Highlights
The number of neurons in the human brain approximates the number of stars in the galaxy
We propose that a signaling cascade from Aβ to tau and PSD-95, involving tau kinases such as PAR-1/microtubule affinity regulating kinases (MARKs) and its activating kinase LKB1, might be involved (Figure 1)
Synapse and dendritic spine pathology have been observed in the early stages of neurodegenerative diseases before neuronal death is evident, suggesting that these cellular locations represent pathogenic sites of action by the disease-causing agents early in the disease process
Summary
The number of neurons in the human brain approximates the number of stars in the galaxy. Information can be stored in the brain by multiple synaptic mechanisms, including altered structure and chemistry of existing synapses, formation of new synapses, or elimination of old ones. Such synaptic plasticity is thought to be fundamental to learning and memory in the brain [9]. Excitatory synapses contain AMPA and NMDA ionotropic glutamate receptors localized on dendritic spines, with basal synaptic transmission largely mediated by the AMPA receptors. High synaptic activity opens NMDA receptors, leading to long-lasting changes in postsynaptic AMPA receptor number and LTP of synaptic transmission [11]. The readers are referred to some excellent previous reviews on the observation of synaptic and dendritic spine pathology in neurological disorders [22,23,24,25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
