The link between brain inflammation, cell growth and division, and neuronal death could provide a target to treat Alzheimer’s and other neurodegenerative disease, research suggests.
The study, “LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction,” appeared in the journal Cell Cycle.
The research team was led by Antonio Giordano, director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia. The study was conducted in collaboration with the University of Siena and the Oncology Research Center of Mercogliano in Naples, both in Italy.
The progressive death of neurons is a hallmark of neurodegenerative diseases like Alzheimer’s, Parkinson’s disease, ALS, and Huntington’s disease. In the case of Alzheimer’s, this programmed neuronal death, called apoptosis, strongly contributes to the memory impairments seen in patients.
Researchers believe that neuronal death is induced by reactivation of the cell cycle, a series of events leading to cell growth and division. Researchers know that Alzheimer’s-affected neurons can re-enter the cell cycle. However, the mechanisms explaining this phenomenon have been poorly understood.
In the healthy brain, mature neurons are in a permanent state of cell cycle arrest. Unlike other cell types throughout the body, neurons do not undergo the processes of cell death and replacement.
Retinoblastoma proteins (RB1/p105, RBL1/p107 and Rb2/p130) have been shown to possess tumor-suppressor activity and to regulate the cellular cycle. Now, the work of Giordano’s team provided a link involving inflammation, cell cycle reactivation, neuronal death, and the production of retinoblastoma proteins, or pRb.
Using an in vitro model of brain inflammation, the authors showed that inflammation induced cell cycle reactivation and ultimately caused neuronal death. These effects were associated with abnormal expression of RBL1/p107 and RB1/p105, suggesting a link between unusual pRb production and reactivation of the cell cycle in neurons.
The study demonstrates that the involvement of pRb in disease goes beyond the field of oncology. Overall, these findings are a clue to better understanding neuronal death and offer a potential therapeutic target to neurodegenerative disorders.
“[Alzheimer’s], similar to other neurodegenerative diseases, is an incurable disorder affecting populations worldwide,” Giordano said in a press release. He said the continued discovery of new mechanisms involved in these disorders may be crucial in successfully treating and preventing 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.