Fate and propagation of endogenously formed Tau aggregates in neuronal cells.

Tau accumulation in the form of neurofibrillary tangles in the brain is a hallmark of tauopathies such as Alzheimer's disease (AD). Tau aggregates accumulate in brain regions in a defined spatiotemporal pattern and may induce the aggregation of native Tau in a prion-like manner. However, the underlying mechanisms of cell-to-cell spreading of Tau pathology are unknown and could involve encapsulation within exosomes, trans-synaptic passage, and tunneling nanotubes (TNTs).

The prion-like spreading of α-synuclein: From in vitro to in vivo models of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. PD is characterized by the loss of dopaminergic neurons, primarily in brain regions that control motor functions, thereby leading to motor impairments in the patients. Pathological aggregated forms of the synaptic protein, α-synuclein (α-syn), are involved in the generation and progression of PD.

α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading.

Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types.

WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers.

Amyloid-β (Aβ) oligomers are a key factor in Alzheimer's disease (AD)-associated synaptic dysfunction. Aβ oligomers block the induction of hippocampal long-term potentiation (LTP) in rodents. The activation of Wnt signaling prevents Aβ oligomer-induced neurotoxic effects.

In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model.

The role of the Wnt signaling pathway during synaptic development has been well established. In the adult brain, different components of Wnt signaling are expressed, but little is known about its role in mature synapses. Emerging in vitro studies have implicated Wnt signaling in synaptic plasticity.

Wnts in adult brain: from synaptic plasticity to cognitive deficiencies.

During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function.

Nicotine prevents synaptic impairment induced by amyloid-β oligomers through α7-nicotinic acetylcholine receptor activation.

An emerging view on Alzheimer disease's (AD) pathogenesis considers amyloid-β (Aβ) oligomers as a key factor in synaptic impairment and rodent spatial memory decline. Alterations in the α7-nicotinic acetylcholine receptor (α7-nAChR) have been implicated in AD pathology. Herein, we report that nicotine, an unselective α7-nAChR agonist, protects from morphological and synaptic impairments induced by Aβ oligomers.

Wnt signaling: role in LTP, neural networks and memory.

Wnt components are key regulators of a variety of developmental processes, including embryonic patterning, cell specification, and cell polarity. The Wnt signaling pathway participates in the development of the central nervous system and growing evidence indicates that Wnts also regulates the function of the adult nervous system. In fact, most of the key components including Wnts and Frizzled receptors are expressed in the adult brain.