eBook: Advancing Neuroscience Research - 10

Pre-formed Fibrils: Another
Perspective in Modelling of
Neurodegenerative Diseases
With many limitations for current disease models, PFFs may be an
efficient, cost-effective strategy.
Introduction
Neurodegenerative diseases inflict a substantial
burden on both personal, societal, and public
health across the globe. These progressive neurological
disorders feature a set of debilitating, incurable
diseases that are increasing in prevalence,
such as Alzheimer's disease (AD) and Parkinson's
disease (PD). Together, both AD and PD afflict over
130 million people worldwide, with its prevalence
rising dramatically with age. This number is only
expected to increase in the foreseeable future as
life spans continue to increase. Unfortunately, neurodegenerative
disease research has been limited
by an inadequate understanding or incomplete
perspective into disease pathology. This, in turn,
has translated into a poor track record in developing
neurodegenerative treatments and discovering
new therapeutic avenues.
Elucidating disease pathology has been heavily
driven through the use of in vitro and in vivo models;
both essential tools in providing new insights
into disease progression, cellular mechanisms, and
much more. In the case of neurodegenerative diseases,
our limited comprehension is in part due to
the use of premature experimental models.1
Existing
neurodegenerative disease models relies on the
use of transgenic mouse models with knock-out or
over-expressed pathogenic genes and proteins.
However, these models often do not completely reproduce
the natural disease progression and are an
incomplete imitation of neurodegeneration. Preformed
fibrils (PFFs) are a novel tool for modeling
AD and PD which are being increasingly used in related
studies. These fibrils are generated in vitro and
can imitate endogenous protein aggregation in
both animal and cellular models. As such, PFFs enable
the creation of a model that more closely aligns
with the traits found in neurodegenerative diseases
including 'seeding' and 'transmission' of the related
pathogenic proteins. In this article, we first discuss
the limitations of current disease models before discussing
in-depth about PFFs and its current applications
in neurodegenerative research.
Current neurodegenerative
disease models
A hallmark of neurodegenerative diseases is protein
misfolding and aggregation of proteins that
results in cellular dysfunction, loss of synaptic connections,
and brain damage. Although the protein
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