Understanding inflammation-induced cell cycle reactivation may prevent neuronal death in neurodegenerative diseases

By Liz Meszaros, MDLinx
Published August 30, 2017

Key Takeaways

Researchers have found that lipopolysaccharide (LPS)—a well-known pro-inflammatory factor that provokes neuronal death by activation of glial cells—may play a role in inducing cell cycle re-entry and/or apoptosis in differentiated neuronal cells, and have published their results in the journal Cell Cycle.

One of the hallmark characteristics of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease, is progressive apoptotic neuronal death. This apoptosis is believed to be triggered by a process of cell cycle reactivation, an early hallmark of neurodegeneration, but the mechanisms of this reactivation are largely unknown.

“Alzheimer’s disease, similar to other neurodegenerative diseases, is an incurables disorder affecting populations worldwide,” said senior author Antonio Giordano, MD, Director of the Sbarro Institute for Cancer Research and Department of Biology, Temple University, Philadelphia,PA.

“However, in recent years, scientists have made great advances in uncovering the cause of these pathologies. As we discover novel elements correlated to the pathways involved in these diseases, we are confident that we will be able to treat and prevent them. Albeit it is still at an early stage, our study brings to light an important aspect of this mechanism that will speed our progress toward this common goal,” he added.

Dr. Giordano and colleagues conducted this study in collaboration with researchers from the University of Siena Italy to assess the effects of LPS-mediated inflammation on cell cycle reactivation and apoptosis of neuronally differentiated cells. They also investigated whether the LPS-mediated inflammatory response had any effects on the function and expression of retinoblastoma (RB) proteins, which have been shown to have tumor suppressor activity and have a central role in cell cycle regulation.

Mature neuronal cells remain in a permanent state of cell cycle arrest and do not undergo the same process of apoptosis and replacement as other tissues in the body. In their in vitro model of brain inflammation, however, Dr. Giordano and colleagues found an aberrant expression of p107 and p105 after inflammatory insult. This inflammation, in turn, induced cell cycle re-entry, causing neuronal cells to resume the cell cycle, and eventually undergo apoptosis, or cell death.

Thus, for the first time, they identified a possible clue to the mechanism for neuronal degeneration, which may be a potential target for therapies for disorders such as Alzheimer’s disease, Parkinson’s disease, ALS, and Huntington’s disease.

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