# The new roles of the autophagy-lysosomal pathway in spinal cord injury-mediated dementia

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $337,459

## Abstract

Project Summary
Recent advances in treatment and management allow many patients suffering a spinal cord injury (SCI) to live
for many years after their traumatic event. Moreover, given increased falls in the elderly, the risk of SCI has
been increasing in that population. Recent evidence, including a large-scale longitudinal population-based
study, indicates that isolated SCI (without concurrent brain injury) are at a high risk of dementia associated with
substantial cognitive impairments. Yet little is known about the mechanisms of SCI-induced dementia or its
relationship to age of onset or age-related neurodegenerative disorders such as Alzheimer’s disease (AD).
This represents an unmet health-care challenge. The autophagy-lysosomal pathway is essential for
intracellular protein and organelle degradation and quality control. Impaired autophagy is strongly implicated in
accumulation of pathological protein aggregates such as phospho-tau tangles and amyloid  plaques and
consequent neuronal cell damage and death in neurodegenerative diseases. Recent data indicate that
perturbation of autophagy can also alter inflammatory responses. Thus, inhibition of autophagy-lysosomal
function could contribute to both neuronal cell damage and inflammation observed in age-related AD/ADRD.
The purpose of this study is to identify the key mechanisms involved in critical yet largely ignored brain
changes after SCI and test the hypothesis that SCI accelerates inhibition of autophagy-lysosomal function in
the brain, ultimately promoting brain neurodegeneration and neuroinflammation and leading to dementia.
 We will use young adult autophagy deficient mice and aged animals to delineate the roles of
autophagy-lysosomal pathway as a key regulator of brain inflammation and neurodegeneration in SCI. Aim 1
will determine whether progressive age-related disruption of the autophagy-lysosomal function in the
brain is accelerated following SCI. Multiple quantitative assessments of autophagy flux, lysosomal function,
inflammation, and neurodegeneration will be combined with characterization of dementia-like functional
outcomes to test the hypothesis that SCI at chronic phase leads to accelerated inhibition of autophagy-
lysosomal function in the brain, contributing to neuroinflammation and neurodegeneration associated with
cognitive decline. Aim 2 will determine the influence of age on the autophagy-lysosomal function in SCI-
mediated dementia. Aged C57BL/6 mice subjected to SCI will be used to address the influence of age on
SCI-mediated dysregulation of the autophagy-lysosomal function, AD-like neuropathology, and
neurodegeneration in the brain, and associated cognitive impairments.
 Since the scope of our current R01 grant is limited to short-term assessment of autophagy-lysosomal
function in the injury site after acute SCI, we request additional funds to collect long-term data necessary to
test this hypothesis. We expect to use these data to support eventual R01 applicatio...

## Key facts

- **NIH application ID:** 10114910
- **Project number:** 3R01NS094527-05S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Junfang Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,459
- **Award type:** 3
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114910

## Citation

> US National Institutes of Health, RePORTER application 10114910, The new roles of the autophagy-lysosomal pathway in spinal cord injury-mediated dementia (3R01NS094527-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114910. Licensed CC0.

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