Determinants of Basal Forebrain Cholinergic Neuron Vulnerability in Parkinson's Disease and Lewy Body Dementia

Abstract

Parkinson's disease (PD) poses one of the greatest healthcare challenges of our time. With the aging of the general population, the incidence of PD is expected to rise in coming decades. This wave will create not only a humanitarian crisis, but an unsustainable tax on societal resources. Although there are effective symptomatic therapies for the motor symptoms of PD (at least in the early stages of the disease), there are not effective therapies for the non-motor, PD and the commonly co-morbid, Lewy body dementia (LBD). This unmet medical need is identified as one of the FY19 PRP Focus Areas - Mechanisms of non-motor symptoms of PD from basic biology to clinical application. This gap in clinical care reflects our poor grasp of disease mechanisms. While it is widely accepted that mitochondrial dysfunction, synucleinopathy and inflammation contribute to PD and LBD, it is far from clear why these disease mechanisms manifest themselves in some neuronal populations and not others. All neurons rely upon proper protein handling. All neurons depend upon mitochondrial function. All neurons appear to be susceptible to the production of inflammatory cytokines and reactive oxygen species by non-neuronal cells. Understanding the basis for this selective vulnerability could provide the insight needed to develop new, potent therapies for nonmotor symptoms in PD. One of the most vulnerable types of neuron in PD, LBD and Alzheimer's disease (AD) is the basal for brain cholinergic neuron (BFCN). Release of acetylcholine (ACh) by BFCNs modulates the activity of large cortical networks, and the degeneration of these neurons is widely thought to be a primary driver of the cognitive deficits accompanying PD, LBD and AD. Yet, very little is known about how or why these neurons should be vulnerable to mitochondrial dysfunction, synucleinopathy or inflammation.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2021
Accession Number
AD1148043

Entities

People

  • Dalton J. Surmeier
  • Jaime Guzman-lucero
  • Tatiana Tkatch
  • Tristano Pancani

Organizations

  • Northwestern University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Alzheimer Disease
  • Astrocytes
  • Biomedical Research
  • Brain
  • Cells
  • Chemical Reactions
  • Confocal Microscopy
  • Data Analysis
  • Dementia
  • Diseases And Disorders
  • Firing Rate
  • Medical Personnel
  • Neurons
  • Neurosciences
  • Parkinson'S Disease
  • Pathology
  • Proteins
  • Stress (Physiology)
  • Universities
  • Vulnerability

Fields of Study

  • Medicine

Readers

  • Economics
  • Neurodegenerative Parkinson's Disease and Rickettsial Disease handbook, including the data level of dopamine, BC, neurons, and PD.
  • Neuroscience