Recent studies in Drosophila have implicated actin cytoskeletal remodeling in myoblast fusion, but the cellular mechanisms underlying this process remain poorly understood. Here we show that actin polymerization occurs in an asymmetric and cell type–specific manner between a muscle founder cell and a fusion-competent myoblast (FCM). In the FCM, a dense F-actin–enriched focus forms at the site of fusion, whereas a thin sheath of F-actin is induced along the apposing founder cell membrane. The FCM-specific actin focus invades the apposing founder cell with multiple finger-like protrusions, leading to the formation of a single-channel macro fusion pore between the two muscle cells. Two actin nucleation–promoting factors of the Arp2/3 complex, WASP and Scar, are required for the formation of the F-actin foci, whereas WASP but not Scar promotes efficient foci invasion. Our studies uncover a novel invasive podosome-like structure (PLS) in a developing tissue and reveal a previously unrecognized function of PLSs in facilitating cell membrane juxtaposition and fusion.

Background: Alzheimer's disease (AD), one of the most common forms of dementia, is a widely studied neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Currently, there is no effective cure available for AD. The astrocyte AQP4 polarized distribution-mediated glymphatic system is essential for Aβ and abnormal tau clearance and is a potential therapeutic target for AD. However, the role of exercise on the AQP4 polarized distribution and the association between the AQP4 polarized distribution and astrocyte phenotype polarization are poorly understood.

Alzheimer’s disease, one of the most common forms of dementia, is characterized by a slow progression of cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered by various side effects and limited efficacy. Despite considerable research, practical treatments for AD have not been developed. Increasing evidence shows that glial cells, especially microglia and astrocytes, are essential in the initiation and progression of AD. During AD progression, activated resident microglia increases the ability of resting astrocytes to transform into reactive astrocytes, promoting neurodegeneration. Extensive clinical and molecular studies show the involvement of microglia and astrocyte-mediated neuroinflammation in AD pathology, indicating that microglia and astrocytes may be potential therapeutic targets for AD. This review will summarize the significant and recent advances of microglia and astrocytes in the pathogenesis of AD in three parts. First, we will review the typical pathological changes of AD and discuss microglia and astrocytes in terms of function and phenotypic changes. Second, we will describe microglia and astrocytes’ physiological and pathological role in AD. These roles include the inflammatory response, “eat me” and “don’t eat me” signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, and demyelination. Last, we will review the pharmacological and non-pharmacological therapies targeting microglia and astrocytes in AD. We conclude that microglia and astrocytes are essential in the initiation and development of AD. Therefore, understanding the new role of microglia and astrocytes in AD progression is critical for future AD studies and clinical trials. Moreover, pharmacological, and non-pharmacological therapies targeting microglia and astrocytes, with specific studies investigating microglia and astrocyte-mediated neuronal damage and repair, may be a promising research direction for future studies regarding AD treatment and prevention.

To Fuse or Not to Fuse?: Cell-cell fusion is poorly understood, although we know that in the nematode, Caenorhabditis elegans , it involves cell-surface fusogens and in the fly, Drosophila , the actin cytoskeleton plays a role. Shilagardi et al. (p. 359 ) reconstituted a high-efficiency, inducible cell-fusion culture system, in which they found that the C. elegans fusogen, Eff-1, induced a low level of cell-cell fusion that was enhanced by coexpression with a cell adhesion molecule, Sticks and stones (Sns), required for myoblast fusion in Drosophila. Sns-enhanced cell-cell fusion was mediated by dynamic actin polymerization that generated invasive membrane protrusions at sites of fusion.

Into the following four groups: (a) control, (b) swim + vehicle, (c) STZ without swim, and (d) swim + STZ. The Barnes maze task and novel object recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) analysis, and related assay kits were used to assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, antioxidant enzymes, amyloid-beta production, and tau hyperphosphorylation. Results Behavioral tests revealed that exercise pretreatment could significantly inhibit STZ-induced cognitive dysfunction (P < 0.05). STZ animals displayed significant loss of presynaptic/postsynaptic markers in the hippocampal CA1 that was reversed by exercise pretreatment (P < 0.05). STZ rats also displayed increased reactive gliosis, release of proinflammatory cytokines, and oxidative damage, effects attenuated by preexercise (P < 0.05, between-treatment changes). Likewise, preexercise significantly induced protein expression (P < 0.001) and DNA-binding activity (P = 0.015) of Nrf2 and downstream antioxidant gene expression in the hippocampal CA1 region (P < 0.05). STZ rats had increased levels of amyloid-beta (1–42) and tau hyperphosphorylation that were significantly ameliorated by exercise (P < 0.05). Histological studies showed that exercise imparted substantial neuroprotection (P < 0.001), suppressing neuronal apoptosis–like cell death in the hippocampal CA1 compared with the STZ control group (P < 0.001). Conclusions Exercise pretraining exerts multifactorial benefits on AD that support its use as a promising new therapeutic option for prevention of neurodegeneration in the elderly and/or AD population....