Sculptor and Destroyer by Mark P. Mattson;

Author:Mark P. Mattson; [Mattson, Mark]
Language: eng
Format: epub
Tags: Addiction; Alzheimer�s disease; AMPA receptor; Amygdala; Amyotrophic lateral sclerosis; Anxiety; Astrocyte; Autism; BDNF (brain-derived neurotrophic factor); CB1 receptor; Dendritic spine; Depression; Dopamine; Engram; Epilepsy; Excitotoxicity; GABAGLP-1; Glucose transporter; Hippocampus; Huntington�s disease; LTP (long-term potentiation); Marijuana; Methamphetamine; Microglia; Nitric oxide; NMDA receptor; Opioid; Optogenetic; Parkinson�s disease; Prefrontal cortex; Presynaptic terminal; Psilocybin; Schizophrenia; Serotonin; Stroke; TBI (traumatic brain injury)
Publisher: MIT Press
Published: 2023-07-12T00:00:00+00:00

Parkinson’s Disease

More than one million people in the United States are currently living with Parkinson’s disease. Someone with this disease experiences progressively worsening difficulty in properly controlling the movement of their limbs. Shakiness of the hands is often the first problem noticed by the patient, although they may also have some difficulty walking and muscle stiffness. These so-called motor manifestations of Parkinson’s disease are a consequence of the degeneration of neurons in the substantia nigra, located in the upper part of the brainstem. The neurons in the substantia nigra that degenerate use the neurotransmitter dopamine, and their activity normally prevents unwanted body movements. During the early stages of the disease, many dopaminergic neurons remain alive but are unable to produce dopamine. The motor symptoms can be relieved by giving levodopa to people with Parkinson’s, a molecule that dopaminergic neurons can convert directly into dopamine. However, levodopa does not slow the degeneration and death of the neurons.

As with Alzheimer’s disease, most cases of Parkinson’s disease occur late in life and have no known genetic cause. The actor and science enthusiast Alan Alda, the evangelist Billy Graham, and the singer Linda Ronstadt are examples of people diagnosed with Parkinson’s when they were in their sixth, seventh, or eighth decade of life (although Ronstadt’s diagnosis was later changed to progressive supranuclear palsy). One risk factor for Parkinson’s disease is a history of head trauma. There is also evidence that repeated exposures to certain pesticides, such as rotenone, can increase one’s risk for Parkinson’s. In chapter 6, you learned about natural and man-made neurotoxins that damage and kill neurons by excitotoxicity. Some of those toxins, such as kainic acid and domoic acid, directly activate glutamate receptors excessively. Others, such as the pesticides rotenone and paraquat, cause excitotoxicity indirectly by impairing the function of mitochondria in neurons. Because of their high firing rates and energy requirements, dopaminergic neurons are particularly vulnerable to such mitochondrial toxins.

The actor Michael J. Fox was diagnosed with Parkinson’s at the age of 29. Developing Parkinson’s at such a young age is uncommon and is usually caused by an inherited gene mutation. From the public record, it is not clear whether one of his parents had early-onset Parkinson’s. According to Wikipedia, Fox believes he may have been exposed to a chemical that caused his Parkinson’s disease: “I used to go fishing in a river near paper mills and eat the salmon I caught; I’ve been to a lot of farms; I smoked a lot of pot in high school when the government was poisoning the crops. But you can drive yourself crazy trying to figure it out.”

Approximately 5 percent of Parkinson’s disease cases are inherited. People with inherited Parkinson’s disease typically begin to exhibit symptoms when they are in their thirties, forties, or fifties. In 1997, geneticists at the US National Institutes of Health reported the identification of a gene mutation associated with inherited Parkinson’s disease in an Italian family (Polymeropoulos et al. 1997). The mutation is inherited in an autosomal

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