An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: a proteomics approach

Abstract

Down syndrome (DS) is one of the most common causes of intellectual disability, due to trisomy of all or part of chromosome 21. DS is also associated with the development of Alzheimer disease (AD) neuropathology after the age of 40 years. To better clarify the cellular and metabolic pathways that could contribute to the differences in DS brain, in particular those involved in the onset of neurodegeneration, we analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls, using a proteomics approach. Proteomics represents an advantageous tool to investigate the molecular mechanisms underlying the disease. From these analyses, we investigated the effects that age, DS, and AD neuropathology could have on protein expression levels. Our results show overlapping and independent molecular pathways (including energy metabolism, oxidative damage, protein synthesis and autophagy) contributing to DS, to aging and to the presence of AD pathology in DS. Investigation of pathomechanisms involved in DS with AD, may provide putative targets for therapeutic approaches to slow the development of AD.

Multiple Herpes Simplex Virus-1 (HSV-1) Reactivations Induce Protein Oxidative Damage in Mouse Brain: Novel Mechanisms for Alzheimer’s Disease Progression

“…Along this line, our redox proteomic approach allowed us to identify 13 HNE adduct proteins profoundly modulated by recurrent HSV-1 infection ( Table 1 ): the majority of these proteins are involved in cellular processes such as energy metabolism (Dhpr, Pgam1, Idh3, and Atp5a1), protein folding (GRP78, Sec23ip), degradation process (Arel1, Lsm11), and cell structure (Dpyl2, Gnb1, Myh10, Ocln, Tpt1). These pathways have been linked to AD onset and progression [ 54 ]. Hence, our data support the hypothesis that oxidative stress conditions induced by HSV-1 reactivation can concur to the virus-induced neurodegeneration.…”

Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism

“…Subsequent studies from the same laboratory led to the identification of proteins involved in energy metabolism and synaptic plasticity, known to be dysfunctional in DS [48–51]. Cenini and co-workers [52] analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls. In this study, the alteration of common pathways between DS and AD pathology including energy metabolism, antioxidant response and proteostasis network have emerged [52].…”

“…Cenini and co-workers [52] analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls. In this study, the alteration of common pathways between DS and AD pathology including energy metabolism, antioxidant response and proteostasis network have emerged [52].…”

Aspectos nutricionais associados ao envelhecimento de indivíduos com síndrome de Down: uma revisão integrativa

“…Estudo de Cenini et al (2015) Em modelos de camundongos com SD, a suplementação de Epigalocatequina-3-galato (EGCG) reduziu ainda a expressão da DYRK1A, enzima cuja superexpressão está associada a déficits cognitivos. A suplementação (9 mg/kg/ day) também reduziu os déficits cognitivos e melhorou a memória e qualidade de vida de pessoas com SD (DE LA TOR-RE et al, 2014).…”