Astrocytes and the Modification of Tau Proteins Contribute to the Advancement of Progressive Supranuclear Palsy
In a groundbreaking study, researchers have shed light on the role of synaptic tau in the progression of Progressive Supranuclear Palsy (PSP), a currently untreatable neurodegenerative disease.
The study reveals that tau, a protein known to accumulate abnormally in PSP, targets synaptic connections. It is discovered that tau spreads through these connections, causing direct damage to synapses and recruiting astrocytes to destroy them. This synaptic tau accumulation is a key mediator of PSP progression, as it impairs synaptic communication and contributes to synapse loss.
The research further suggests that clusterin, a protein previously linked to Alzheimer's disease, interacts with tau in postsynaptic terminals of PSP synapses. Super-resolution imaging shows clusterin colocalized with tau in synapses, indicating a potential binding relationship.
The findings also demonstrate that oligomeric tau can enter live human postsynapses, contributing to synaptic damage. This synaptic spread mechanism helps explain how tau pathology progressively advances through different brain regions connected by synapses, leading to the characteristic decline in motor and cognitive function seen in PSP.
Given these insights, targeting synaptic tau presents a promising therapeutic strategy. Interventions aimed at reducing tau accumulation at synapses, inhibiting tau’s trans-synaptic spread, or protecting synapses from astrocytic engulfment could potentially slow or halt disease progression by preserving neural circuit integrity.
The approach is supported by live human brain slice models exposing synapses to PSP tau, which confirm that tau toxicity at synapses triggers pathological changes and synapse elimination.
The findings offer hope to patients with PSP, suggesting that the disease may involve dynamic processes that could be modified. Proteomics showed increased clusterin in synapses in PSP brains, adding another layer of complexity to the disease's pathology and potential treatment strategies.
In conclusion, tau-mediated synaptic damage contributes to PSP progression by synapse dysfunction and loss, facilitation of tau propagation, and recruitment of astrocytic synapse clearance mechanisms. Therapeutic efforts focused on synaptic tau hold significant potential to mitigate these pathogenic processes in PSP.
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- The new research on Progressive Supranuclear Palsy (PSP) has highlighted that inflammation caused by tau, a protein that abnormally accumulates in PSP, damages synapses by targeting synaptic connections.
- The study also reveals that oligomeric tau can infiltrate live human postsynapses, causing synaptic damage and contributing to the progressive advancement of tau pathology in the brain.
- The emerging neuroscience news about PSP indicates that clusterin, a protein previously linked to Alzheimer's disease, interacts with tau in postsynaptic terminals of PSP synapses, potentially contributing to synaptic damage.
- According to the recent findings, attentional and cognitive impairments in PSP could be due to the direct impact of tau on synaptic connections, leading to communication impairment and synaptic loss.
- As aging is a risk factor for neurodegenerative diseases like PSP, this research emphasizes the importance of understanding the role of neurology, particularly in regards to synaptic tau and its implications for health-and-wellness and medical-conditions like neurological-disorders.
- The study adds to the growing body of neuroscience knowledge about PSP, providing insights into potential treatment strategies that focus on preserving synapse integrity, such as reducing tau accumulation, inhibiting tau trans-synaptic spread, or protecting synapses from astrocytic engulfment.
