Development of a methodology for large-scale production of prions for biological and structural studies.

Prion diseases are a group of infectious neurodegenerative diseases produced by the conversion of the normal prion protein (PrP) into the disease-associated form (PrP). Extensive evidence indicate that the main or sole component of the infectious agent is PrP, which can replicate in affected individuals in the absence of nucleic acids. However, the mechanism of PrP-to-PrP conversion remains elusive, which has been attributed to the lack of sufficient structural information of infectious PrP and a reliable system to study prion replication .

Extensive accumulation of misfolded protein aggregates during natural aging and senescence.

Accumulation of misfolded protein aggregates is a hallmark event in many age-related protein misfolding disorders, including some of the most prevalent and insidious neurodegenerative diseases. Misfolded protein aggregates produce progressive cell damage, organ dysfunction, and clinical changes, which are common also in natural aging. Thus, we hypothesized that aging is associated to the widespread and progressive misfolding and aggregation of many proteins in various tissues.

Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged.

Peripheral Delivery of Neural Precursor Cells Ameliorates Parkinson's Disease-Associated Pathology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of motor control due to a wide loss of dopaminergic neurons along the nigro-striatal pathway. Some of the mechanisms that contribute to this cell death are inflammation, oxidative stress, and misfolded alpha-synuclein-induced toxicity. Current treatments are effective at managing the early motor symptoms of the disease, but they become ineffective over time and lead to adverse effects.

Prion disease is accelerated in mice lacking stress-induced heat shock protein 70 (HSP70).

Prion diseases are a group of incurable neurodegenerative disorders that affect humans and animals via infection with proteinaceous particles called prions. Prions are composed of PrP, a misfolded version of the cellular prion protein (PrP). During disease progression, PrP replicates by interacting with PrP and inducing its conversion to PrP As PrP accumulates, cellular stress mechanisms are activated to maintain cellular proteostasis, including increased protein chaperone levels.

Modeling amyloid beta and tau pathology in human cerebral organoids.

The typical abnormalities observed in the brain of Alzheimer's disease (AD) patients include synaptic alterations, neuronal death, brain inflammation, and the accumulation of protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Despite the development of many animal and in vitro models for AD, there is a lack of an experimental approach that fully recapitulates essential aspects of the disease in human cells. Here, we report the generation of a new model to study AD, consisting of cerebral organoids (COs) produced from human-induced pluripotent stem cells (iPSCs).

Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells.

Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients.

HIV/AIDS: modified stem cells in the spotlight.

Since HIV/AIDS was first recognized in 1981, an urgent need has existed for the development of novel therapeutic strategies to treat the disease. Due to the current antiretroviral therapy not being curative, human stem cell-based therapeutic intervention has emerged as an approach for its treatment. Genetically modified hematopoietic stem cells (HSCs) possess the potential to self-renew, reconstitute the immune system with HIV-resistant cells, and thus control, or even eliminate, viral replication.