Aging and Neurodegeneration
The laboratory has developed studies over the last years on the mechanisms of brain aging and neurodegeneration, particularly those involving the intraneuronal pigment known as neuromelanin.
This pigment is stored inside specific organelles along with proteins, lipids and metals and mainly accumulates as a function of age in dopaminergic and noradrenergic brain areas that selectively degenerate in Parkinson’s and Alzheimer’s diseases. The aim of research activity is then the study of structure, biosynthesis and interaction of neuromelanin with metals, as well as its role in mechanisms of brain aging and neurodegeneration.
The research activity focuses on the study of biosynthetic mechanisms of specific intraneuronal organelles containing neuromelanin, proteins, lipids and metals. It is important to understand the role of these organelles that accumulate inside neurons during aging and their influence on neuronal vulnerability.
Although the accumulation of neuromelanin in brain aging occurs in various brain areas, the most heavily pigmented ones are those that selectively degenerate during Parkinson’s disease. Since aging is the main risk factor for the disease, it is important to study these cellular mechanisms and their correlated alterations in brain aging that could increase neuronal vulnerability.
The characterization of human neuromelanin allowed the design and synthesis (in collaboration with other groups) of various synthetic neuromelanins mimicking the structure of human brain pigment. Neuromelanin models were prepared by mixing main elements of human neuromelanin: melanic portion derived by catecholamines, proteins and iron ions.
These new compounds may have dual application:
- can be used in in vitro and in vivo models of Parkinson’s disease since these compounds can mimic typical neuroinflammatory and neurodegenerative mechanisms of the disease;
- can be used to study the role of neuromelanin and iron in relaxation and saturation processes of magnetic resonance imaging.
Recently, neuromelanin-sensitive magnetic resonance imaging techniques have been found to provide notable contrast between substantia nigra and locus coeruleus (regions with highest levels of neuromelanin content) and the surrounding brain areas. These new techniques can provide semi-quantitative data on the physiology of brain areas differently affected during the disease, with different degrees of neuronal death (then neuromelanin depletion), and therefore can be used to early diagnose Parkinson’s and Alzheimer’s disease.
The laboratory is studying the role of neuromelanin and iron in relaxation and saturation processes of magnetic resonance imaging by using different types of neuromelanin models. Simultaneously, in collaboration with other groups, we are studying the correlation between imaging data and the contents of neuromelanin and iron. This will allow the in vivo quantification of neuromelanin concentration, as reliable marker for function of catecholamine system, whose alterations are involved in neuropsychiatric and neurodegenerative diseases.