Parkinson’s Disease: Alpha Synuclein, Heme Oxygenase and Biotherapeutic Countermeasures

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Abstract

Neurodegenerative disorders have been and remain persistent sources of enormous suffering throughout
human history. The tragedy of their impact on human relationships, physical vitality, and fundamental dignity
cannot be understated. Parkinson’s disease (PD), one of the most common of these terrible illnesses, has a global
incidence of approximately two-to-four percent of the human population, along with devastating social and economic
impact. The present review analyzes aspects of PD pathophysiology that offer particularly attractive strategies
for the development of improved prevention and therapy. The occurrence, symptoms, pathogenesis, and
etiology of PD are considered, with focus on how the Alpha synuclein protein, which normally regulates neurotransmitter
release, is aggregated by oxidative stressors into toxic inclusions, prominently including Lewy bodies
and insoluble fibrils that disrupt the organization of brain areas responsible for motor control. The contribution to
a progressively prooxidant tissue environment resulting from interaction between advanced glycation end
products (AGEs) and their cognate receptors (RAGEs) is examined here as a significant driver of PD. This review
also explores strategies currently being developed by a U.S.-Russian team that may reduce the risk and severity of
PD by use of recombinant atoxic derivatives (ad) of botulinum neurotoxins (BoNT/A ad), that traffic inducers of
the cytoprotective enzyme heme oxygenase to selected midbrain neurons, at which Alpha synuclein aggregation
occurs. Considered together, the topic material presented here provides both researchers and clinicians with a
short but concise overview of the current understanding of PD pathology and approaches to biotherapeutic
(precision) countermeasures to its onset and progression.
Original languageEnglish
Article number2018
Pages (from-to)1-5
Number of pages5
JournalCurrent Pharmaceutical Design
Volume24
Issue number2018
StatePublished - 16 Jul 2018

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