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As the global population ages, the incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that β-amyloid protein (Aβ) deposition is a key factor leading to AD. However, the clinical efficacy of treating AD with anti-Aβ protein antibodies is not satisfactory, suggesting that Aβ amyloidosis may be a pathological change rather than a key factor leading to AD. Identification of the causes of AD and development of corresponding prevention and treatment strategies is an important goal of current research. Following the discovery of soluble oligomeric forms of Aβ (AβO) in 1998, scientists began to focus on the neurotoxicity of AβOs. As an endogenous neurotoxin, the active growth of AβOs can lead to neuronal death, which is believed to occur before plaque formation, suggesting that AβOs are the key factors leading to AD. PANoptosis, a newly proposed concept of cell death that includes known modes of pyroptosis, apoptosis, and necroptosis, is a form of cell death regulated by the PANoptosome complex. Neuronal survival depends on proper mitochondrial function. Under conditions of AβO interference, mitochondrial dysfunction occurs, releasing lethal contents as potential upstream effectors of the PANoptosome. Considering the critical role of neurons in cognitive function and the development of AD as well as the regulatory role of mitochondrial function in neuronal survival, investigation of the potential mechanisms leading to neuronal PANoptosis is crucial. This review describes the disruption of neuronal mitochondrial function by AβOs and elucidates how AβOs may activate neuronal PANoptosis by causing mitochondrial dysfunction during the development of AD, providing guidance for the development of targeted neuronal treatment strategies.

Tissues and organs undergo structural deterioration and functional decline during aging. DNA damage is considered a major cause of stem cell senescence. Although stem cells develop sophisticated DNA repair systems, when the intrinsic and extrinsic insults exceed the DNA repair capacity, cellular senescence, and age-related diseases inevitably occur. Therefore, the prevention and alleviation of DNA damage is an alternative to DNA repair in attenuating stem cell senescence and preventing age-related diseases. Pre-B-cell leukaemia homeobox 1 (PBX1) participates in maintaining the pluripotency of human embryonic and haematopoietic stem cells. Our recent studies showed that PBX1 promotes hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation, decreases cellular senescence and apoptosis, and enhances induced pluripotent stem cell generation. Whether PBX1 attenuates HF-MSC senescence and apoptosis by alleviating DNA damage or by enhancing DNA repair remains unknown. In this study, we aimed to determine the effects of PBX1 on the intrinsic ROS or extrinsic H2O2-induced cellular senescence of HF-MSCs. To this end, we generated HF-MSCs overexpressing either PBX1, or poly (ADP-ribose) polymerase 1, or both. Our results showed that PBX1 overexpression attenuates HF-MSC senescence and apoptosis by alleviating reactive oxygen species (ROS)-mediated DNA damage instead of enhancing DNA repair. This is the first study to report that PBX1 attenuates stem cell senescence and apoptosis by alleviating DNA damage. It provides new insight into the mechanism of stem cell senescence and lays the foundation for the development of strategies for age-related disease prevention and treatment, and in particular, hair follicle repair and regeneration.

Autophagy is an evolutionarily conserved vacuolar process functioning in the degradation of cellular components for reuse. In plants, autophagy is generally activated upon stress and its regulation is executed by numbers of AuTophaGy-related genes (ATGs), of which the ATG8 plays a dual role in both biogenesis of autophagosomes and recruitment of ATG8-interacting motif (AIM) anchored selective autophagy receptors (SARs). Such motif is either termed as AIM or ubiquitin-interacting motif (UIM), corresponding to the LC3-interacting region (LIR)/AIM docking site (LDS) or the UIM docking site (UDS) of ATG8, respectively. To date, dozens of AIM or UIM containing SARs have been characterized. However, the knowledge of these motifs is still obscured. In this review, we intend to summarize the current understanding of SAR proteins and discuss the conservation and diversification of the AIMs/UIMs, expectantly providing new insights into the evolution of them in various biological processes in plants.

As the global population ages, the incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that b-amyloid protein (Ab) deposition is a key factor leading to AD. However, the clinical efficacy of treating AD with anti-Ab protein antibodies is not satisfactory, suggesting that Ab amyloidosis may be a pathological change rather than a key factor leading to AD. Identification of the causes of AD and development of corresponding prevention and treatment strategies is an important goal of current research. Following the discovery of soluble oligomeric forms of Ab (AbO) in 1998, scientists began to focus on the neurotoxicity of AbOs. As an endogenous neurotoxin, the active growth of AbOs can lead to neuronal death, which is believed to occur before plaque formation, suggesting that AbOs are the key factors leading to AD. PANoptosis, a newly proposed concept of cell death that includes known modes of pyroptosis, apoptosis, and necroptosis, is a form of cell death regulated by the PANoptosome complex. Neuronal survival depends on proper mitochondrial function. Under conditions of AbO interference, mitochondrial dysfunction occurs, releasing lethal contents as potential upstream [ABSTRACT FROM AUTHOR]