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Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
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Dihydrotestosterone in Amyotrophic lateral sclerosis-The missing link?

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  • 1Neurology Division, Department of Medicine, Government Medical college and Hospital, Chandigarh, India.

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|October 13, 2020
PubMed
Summary

Lower levels of dihydrotestosterone (DHT) are linked to Amyotrophic Lateral Sclerosis (ALS). This suggests a potential "testosterone resistance" at the blood-brain barrier may contribute to motor neuron death in ALS patients.

Keywords:
Amyotrophic Lateral SclerosisCerebrospinal fluidLuteinizing hormoneblood-brain barrierdihydrotestosteronesex hormone binding globulin

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Area of Science:

  • Neuroscience
  • Endocrinology

Background:

  • Testosterone's role in Amyotrophic Lateral Sclerosis (ALS) causation is under investigation.
  • Alterations in androgen levels may be implicated in neurodegenerative processes.

Purpose of the Study:

  • To investigate cerebrospinal fluid (CSF) levels of free testosterone and dihydrotestosterone (DHT) in ALS patients compared to controls.
  • To explore the potential link between specific androgens and ALS pathogenesis.

Main Methods:

  • CSF samples were collected from 13 ALS patients (7 males, 6 females) and 22 controls (12 males, 10 females).
  • Levels of free testosterone and DHT were quantified in the CSF of all participants.

Main Results:

  • No significant difference in CSF free testosterone levels was observed between ALS patients and controls.
  • CSF DHT levels were significantly decreased in both male and female ALS patients compared to controls.

Conclusions:

  • Reduced DHT levels may be integral to motor neuron survival, with deficiency potentially leading to ALS.
  • A possible "testosterone resistance" at the blood-brain barrier, potentially due to dysfunctional transport proteins, may limit central nervous system androgen availability in ALS.
  • This mechanism could explain elevated peripheral testosterone and associated physical traits in ALS patients, ultimately contributing to motor neuron degeneration.