Physiological and pathological insights into exosomes in the brain

Exosomes are small vesicles secreted by all cell types in the brain and play a role in cell-cell communication through the transfer of cargo or encapsulation.Exosomes in the brain have considerable impact on neuronal development,activation,and regeneration.In addition,exosomes are reported to be involved in the onset and propagation of various neurodegenerative diseases.In this review,we discuss the content of exosomes derived from major cell types in the brain,and their function under physiological and pathological conditions.

Defining activation states of microglia in human brain tissue: an unresolved issue for Alzheimer's disease

The development of concepts concerning the role of microglia in different brain diseases has relied on studies of animal models or human brain tissue,which primarily use antibodies and immunohistochemistry techniques to make observations.Since initial studies defined increased expression of the major histocompatibility complexⅡprotein human leukocyte antigen-DR as a means of identifying reactive,and therefore by implication,damage-causing microglia in Alzheimer's disease(AD)or Parkinson's disease(PD),understanding and describing their activation states has evolved to an unexpected complexity.It is still difficult to ascertain the specific functions of individual microglia,particularly those associated with pathological structures,using a narrow range of antigenic markers.As many approaches to developing treatments for AD or PD are focused on anti-inflammatory strategies,a more refined understanding of microglial function is needed.In recent years,gene expression studies of human and rodent microglia have attempted to add clarity to the issue by sub-classification of messenger RNA expression of cell-sorted microglia to identify disease-associated profiles from homeostatic functions.Ultimately all newly identified markers will need to be studied in situ in human brain tissue.This review will consider the gaps in knowledge between using traditional immunohistochemistry approaches with small groups of markers that can be defined with antibodies,and the findings from cell-sorted and single-cell RNA sequencing transcription profiles.There have been three approaches to studying microglia in tissue samples:using antigenic markers identified from studies of peripheral macrophages,studying proteins associated with altered genetic risk factors for disease,and studying microglial proteins identified from mRNA expression analyses from cell-sorting and gene profiling.The technical aspects of studying microglia in human brain samples,inherent issues of working with antibodies,and findings of a range of different functional microglial markers will be reviewed.In particular,we will consider markers of microglia with expression profiles that do not definitively fall into the pro-inflammatory or anti-inflammatory classification.These additional markers include triggering receptor expressed on myeloid cells-2,CD33 and progranulin,identified from genetic findings,colony stimulating factor-1 receptor,purinergic receptor P2RY12,CD68 and Toll-like receptors.Further directions will be considered for addressing crucial issues.

APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation

Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.

Mini review: linkage between α-Synuclein protein and cognition

α-synuclein is a protein that plays important roles in cognitive function in the normal brain,although its exact role is not fully understood.However,current studies reveal that defects inα-synuclein function could contribute to various neurodegenerative disorders,such as Parkinson’s disease(PD),a disease with symptomatic progression of deterioration in motor and cognitive function.Recent studies show that the level ofα-synuclein in cerebrospinal fluid(CSF)is highly correlated with speed of cognitive decline,suggesting a potential role ofα-synuclein in cognitive function.In this mini review,we will be focus on literatures ofα-synuclein in cognitive function in the non-diseased brain,as well as the impact that defectiveα-synuclein has on cognition in disease brain.This will be accomplished by assessing the effects of solubleα-synuclein,α-synuclein oligomers,and extracellularα-synuclein transport,on neurodegeneration.