FE65:a hub for neurodevelopment

FE65,initially identified as a binding partner of amyloid precursor protein(APP),is an adaptor protein enriched in the brain and regulated during development.FE65 belongs to the FE65 protein family.This family is comprised of three members,FE65,FE65 like-1(FE65L1),and FE65 like-2(FE65L2).

Regulation of cytohesins by their interactors in the nervous system

Adenosine diphosphate ribosylation factors(ARFs) are small GTP-binding proteins of the Ras superfamily which are involved in membrane trafficking and actin cytoskeleton remodeling.Like other small GTPases,their functions are attributed to the cycling of ARF between GTP(active) and GDP (inactive) states through the actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins,respectively.

The roles of atypical protein kinase Cs(aPKCs) in the nervous system: targets for neuroregeneration?

The protein kinase C(PKC)family:PKC family is a subgroup of the AGC serine-threonine kinases that consists of 10 distinct members in mammals(Spitaler and Cantrell,2004).They all contain a C-terminal catalytic domain that is connected to the N-terminal regulatory domains.PKCs are subdivided into three classes according to their structures and activators.The classical/conventional PKC isoforms possess tandem C1 domains that bind to their well-known activators diacylglycerol and phorbol esters and also contain a C2 domain that mediates the binding of Ca^2+-sensitive anionic phospholipids.

Emerging roles of the neural adaptor FE65 in neurite outgrowth

The brain is the third largest organ in the human body and consists of over80 billion neurons（Herculano-Houzel,2009）.Neurons are interconnected by neurite to form a complex neural network that allows the communication of neurons to regulate different body functions and activities.Neurites,body.

Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer’s disease

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the brain.The overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of AD.Apparently,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD.Recently,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ligands.Here,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD mice.The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of Cory-B.Notably,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.