# Role of Inflammation and Oxidative Stress in Parkinson's Disease

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2022 · —

## Abstract

Aging and Parkinson's disease (PD). Aging is the primary risk factor for PD. Despite reported success
with neurotrophic or neuroprotective therapeutic drugs or cell replacement therapies in animal models of
PD, none have led to a clinically effective treatment avenue, curing all aspects of the disease complex.
Since aging is the number one risk factor for PD, it must be considered in designing appropriate animal
models. The studies proposed herein are unique in that we utilize aging as an important aspect of
our models, many studies have shown that the aged “environment” may be a critical factor in
response to therapeutics.
 Inflammation and Parkinson’s disease. Inflammation in the brain, in particular, activation of microglia
has been increasingly associated with the ongoing pathogenesis of PD, as well as several other
neurodegenerative disorders. An area that has not been widely considered is that innate immune function
is profoundly impacted by aging. We have demonstrated profound changes in proteomic profiles of
microglia with age, and others have examined genomic alterations as well. We have recently demonstrated
that some anti-inflammatory approaches to treat PD models that are successful in young animals, are not
as efficacious in aged animals. Pointing to an important role of aging as a factor involved in disease
progression and the response to therapeutics.
 Exosomes are powerful genomic modulators of inflammation: Human adipose-derived stem cells
(hASC’s) manifest a secretome that is capable of modulating the environment of the host. Among these secreted
molecules, small membrane-bound vesicles known as exosomes can modulate immune function as part of their
mechanism of action following both brain injury and epilepsy. Exosomes contain long non coding RNA (lncRNA)
that act as genomic modulators. Exosomes are an ideal vector for delivery of neuroprotective agents because
of their unique ability to hone to tissues, and their increased stability compared to un-encapsulated RNA. Further,
we have evidence that they modulate inflammation at the genomic level, making them a powerful tool to explore
as a therapeutic in PD
 Aging impacts microglial phenotype, reducing the efficacy some therapeutics. It is our hypothesis, that
hASC exosomes alter microglial function at a genomic level by delivery of lncRNA metastasis associated
lung adenocarcinoma transcript 1 (MALAT1), and other important factors, thus making them ideal for use in
aged subjects. We will explore this by isolating microglia from young and aged rats, treated with and without
intranasal hASC exosomes and perform advanced mass spectrometry based phenotypic profiling. We will
characterize microglia proteomic profiles during progression of an AAV9-a-synuclein model of PD in young
and aged rats.
 We hypothesize that hASDCexo will modulate the progression of PD pathology by interacting with the
innate immune system at the genomic level. Many therapeutic approaches focused on altering inna...

## Key facts

- **NIH application ID:** 10456015
- **Project number:** 5I01BX000231-11
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** PAULA C BICKFORD
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2009-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456015

## Citation

> US National Institutes of Health, RePORTER application 10456015, Role of Inflammation and Oxidative Stress in Parkinson's Disease (5I01BX000231-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10456015. Licensed CC0.

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