It is estimated that more than six million people in the United States
suffer from some kind of degenerative neurological condition including
Parkinson's Disease (PD).
Despite advances in surgical techniques, cataracts remain a
significant cause of world blindness. It is estimated that any therapy
that could delay the onset of cataracts by just 10 years, could reduce
the number of cataract surgeries annually by half, and moreover, improve
the quality of visual health care while reducing costs.
‘Parkin plays a direct role in the prevention of oxidative stress through its ability to maintain cellular mitochondrial populations.’
Although mutations in the PARK2 gene that encodes the Parkin protein
are associated with developing early-onset Parkinson's disease,
much remains to be discovered about how Parkin functions in cells and
how loss of Parkin function could contribute to PD and other
Parkin is known to regulate the degradation of
mitochondria that are cellular organelles that generate energy required
for a multitude of cellular functions. Damage to mitochondria is
associated with the production of free radicals during the aging process
and is involved in the development of multiple diseases ranging from
neurodegenerative diseases to cataract formation.
To discover new cellular functions for Parkin and how loss of Parkin
function could contribute to age-related diseases, a team of
researchers in the Charles E. Schmidt College of Medicine at Florida
Atlantic University engineered eye lens cells to make either normal
Parkin or a mutant form of Parkin, and examined whether Parkin function
was required for lens cell mitochondrial function, and lens cell
Results of the study, recently published in the journal Biochemica et Biophysica Acta: Molecular Basis of Disease
are the first to demonstrate that the Parkin gene is turned on when
cells are exposed to environmental insults that cause free radical
formation and cataract formation. They also discovered that through the
removal of mitochondria that are damaged by these environmental insults,
Parkin prevents free radical formation in lens cells and increases the
ability of the cells to survive exposure to conditions that are
associated with aging and the development of many degenerative diseases.
The data suggest an important function for Parkin in promoting the
survival of not only lens cells, but of many cells of the body including
neurons, and they suggest that activation of the Parkin gene could
prevent cell damage that is associated with age-related cataract
formation and death of neurons associated with PD and other age-related
"We found that Parkin is necessary to maintain lens cell function
and that loss of Parkin function likely contributes to the formation of
cataracts and possibly other age-related degenerative diseases that are
associated with loss of mitochondrial function and increased free
radical formation," said Marc Kantorow, senior-author, professor
of biomedical science, and assistant dean of graduate programs in FAU's
Charles E. Schmidt College of Medicine.
"Our findings suggest that
Parkin plays a direct role in the prevention of oxidative stress through
its ability to maintain cellular mitochondrial populations. Our data
also suggests that the gene encoding Parkin is induced upon
environmental damage so that drugs or genetic methods to increase Parkin
levels and function could prove effective in the prevention of
cataracts and other age-related degenerative diseases including
neurological diseases like Parkinson disease."
Kantorow and co-authors Lisa Ann Brennan, research associate
professor in FAU's College of Medicine, and Josef Khoury, a Master's
degree student in the Kantorow Laboratory, hypothesized that Parkin also
may be important for the embryonic development of the eye lens since
regulation of mitochondrial function is a key feature of the development
of all tissues.
"We found that levels of Parkin based on genomic sequencing of eye
lens at different growth stages exhibited different levels of Parkin
suggesting that Parkin had region-specific functions in the eye lens,"
said Brennan. "We were looking for genes that are changed during the
normal growth and differentiation of lens cells to help identify those
genes that control how undifferentiated stem-like cells become mature
transparent eye lens cells."
"The next step of our ongoing research is to work to establish how
Parkin regulates the growth and development of the eye lens by
controlling mitochondrial populations that are required for lens cell
growth," said Kantorow. "We want to be able to identify the genetic
mechanisms that regulate the production of Parkin in cells and to see if
they can be manipulated to increase Parkin levels, thereby increasing
cell survival to prevent disease."