What are Neurodegenerative Diseases ?
Brain Health Awareness Series
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This article will dive into the world of Neurodegenerative Diseases (NDs), exploring the mysteries of the Brain, and the follow-up article will uncover the ways by which we can delay the onset and progression of NDs.
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1. Definition of Neurodegenerative Diseases (NDs)
The word Neurodegenerative is composed of the prefix “neuro-,” which designates nerve cells (i.e., neurons), and “degeneration,” which refers to, in the case of tissues or organs, a process of losing structure or function.
Neurodegenerative diseases are a group of conditions that affect the brain and nervous system. They cause a progressive decline in the function of nerve cells, leading to problems with movement, thinking, and behavior. In simple terms, these diseases occur when brain cells become damaged and eventually die.
Humans are living longer, and with that, suffering a higher burden of Neurodegenerative Diseases. Aging is one of the most significant risk factors for many Neurodegenerative Diseases.
2. Importance of Understanding NDs
NDs such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS) affect millions of people worldwide. According to the World Health Organization, around 50 million people worldwide had dementia in 2021, with Alzheimer's disease being the most common form. By 2050, the number of people living with dementia is expected to triple, reaching around 152 million.
Meanwhile, Parkinson's disease affects around 6 million people globally, and this number is also projected to rise as the population ages.
A better understanding of the risk factors and underlying causes of NDs can help develop prevention strategies, such as lifestyle modifications and early interventions, to reduce the incidence of these diseases.
Increased awareness and understanding of NDs can lead to better support systems for affected individuals and their families, as well as inform public health policies and resource allocation.
3. Different types of NDs
Common neurodegenerative diseases include Alzheimer's, Parkinson's, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). Besides these common ones, there are also different rare form of NDs which are displayed in the Figure below:
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Before reading further please refer to Supplementary Article: it covers the Anatomy of brain, Functional unit of brain and nervous system - Neuron, How neurons communicate with each other and Some more interesting facts about brain.
To better understand NDs, it is essential to first learn the basics of the brain and the nervous system, as they are the primary areas affected by these disorders.
4. Characteristic Features of different NDs
4.1 Alzheimer's disease (AD):
Cognitive decline: Memory loss, confusion, and problems with reasoning and decision-making.
Behavioral and emotional changes: Depression, anxiety, agitation, and mood swings.
4.2 Parkinson's disease (PD):
Impaired movement: Tremors, muscle stiffness, slow movements, and difficulty with balance and coordination.
Cognitive decline: Mild to moderate cognitive impairment, with some patients developing dementia.
4.3 Huntington's disease (HD):
Impaired movement: Involuntary movements (chorea), muscle stiffness, and problems with balance and coordination.
Cognitive decline: Impaired judgment, memory loss, and difficulties with planning and decision-making.
Behavioral and emotional changes: Depression, irritability, and mood swings.
4.4 Amyotrophic lateral sclerosis (ALS):
Impaired movement: Progressive muscle weakness and stiffness, leading to difficulties in speaking, swallowing, and breathing.
Cognitive decline: Some patients may develop frontotemporal dementia, with symptoms like language problems and changes in personality and behavior.
4.5 Frontotemporal dementia:
Cognitive decline: Problems with language, behavior, and executive function.
Behavioral and emotional changes: Apathy, disinhibition, and compulsive behaviors.
Communication difficulties: Progressive language problems, including speaking, understanding, and reading.
4.6 Multiple System Atrophy:
Impaired movement: Muscle stiffness, tremors, and problems with balance and coordination.
Autonomic dysfunction: Difficulty controlling blood pressure, bladder, bowel, and sexual function.
5. Different types of Neurotansmitters and their role in NDs
Acetylcholine is an excitatory neurotransmitter because it generally makes cells more excitable. It governs muscle contractions and causes glands to secrete hormones.
Alzheimer’s disease, which initially affects memory formation, is associated with a shortage of acetylcholine.
Glutamate is a major excitatory neurotransmitter. Too much glutamate can kill or damage neurons and has been linked to disorders including Parkinson's disease, stroke, seizures, and increased sensitivity to pain.
GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter that helps control muscle activity and is an important part of the visual system. Drugs that increase GABA levels in the brain are used to treat epileptic seizures and tremors in patients with Huntington’s disease.
Serotonin is a neurotransmitter that constricts blood vessels and brings on sleep. It is also involved in temperature regulation. Low levels of serotonin may cause sleep problems and depression, while too much serotonin can lead to seizures.
Dopamine is an inhibitory neurotransmitter involved in mood and the control of complex movements. The loss of dopamine activity in some portions of the brain leads to the muscular rigidity of Parkinson’s disease.
6. Common Mechanisms of Neurodegeneration
Neurodegeneration is a complex process involving multiple mechanisms that contribute to the progressive loss of neuronal structure and function. Some common mechanisms of neurodegeneration include:
Oxidative stress: The imbalance between the production of reactive oxygen species (ROS) and the ability of cells to detoxify these reactive molecules can lead to oxidative damage of cellular components, including lipids, proteins, and DNA. This damage can impair cellular function and contribute to neuronal death.
Mitochondrial dysfunction: Mitochondria are essential for energy production and play a crucial role in maintaining neuronal function.
Impairment of mitochondrial function can result in energy deficiency, increased oxidative stress, and activation of cell death pathways, all of which contribute to neurodegeneration.
Neuroinflammation: Chronic activation of the immune system in the central nervous system, particularly involving microglia and astrocytes, can result in the release of pro-inflammatory cytokines and other inflammatory molecules.
This inflammation can exacerbate neuronal damage and contribute to the progression of neurodegenerative diseases.
Genetic factors: Mutations or variations in specific genes can lead to the development of some neurodegenerative diseases or increase the risk of developing them.
These genetic factors can influence various aspects of cellular function, including protein synthesis, folding, and degradation.
Environmental factors: Exposure to certain toxins, infections, or other environmental factors can contribute to the development or progression of some neurodegenerative diseases by interacting with genetic factors or directly damaging neurons.
7. Which Brain regions are majorly affected in different NDs ?
These disorders jeopardize the normal functioning of the brain and lead to the progressive decline or even the complete loss of sensory, motor, and cognitive function.
Alzheimer's disease: Primarily affects the hippocampus and other regions associated with memory and learning.
Parkinson's disease: Primarily affects dopaminergic neurons in the substantia nigra, which is involved in movement control.
Huntington's disease: Primarily affects medium spiny neurons in the striatum, which is involved in movement and cognition.
Amyotrophic Lateral Sclerosis: Primarily affects motor neurons in the brain and spinal cord, which control muscle movement.
Frontotemporal dementia: Primarily affects the frontal and temporal lobes of the brain, which are involved in language, behavior, and emotional regulation.
Multiple system atrophy: Primarily affects multiple brain regions and systems, including the basal ganglia, cerebellum, and autonomic nervous system.
8. Protein aggregate deposition also affects the nervous system
Many neurodegenerative diseases are characterized by the accumulation of misfolded proteins, which can form toxic aggregates or inclusions within cells.
Alzheimer's disease: Accumulation of beta-amyloid plaques and tau protein tangles in the brain.
Parkinson's disease: accumulation of alpha-synuclein protein in Lewy bodies within neurons
Huntington's disease: misfolded Huntington protein in HD,
Amyotrophic Lateral Sclerosis: aggregation of ubiquitinated proteins in amyotrophic lateral sclerosis
Evidence suggests that the spread of misfolded protein from cell-to-cell significantly contributes to the progression of disease. Moreover, in many cases, these misfolded proteins invade healthy brain tissue when two of these affected cells are placed together.
These NDs are challenging to treat and scientists are working hard to discover better treatment strategies to fight these debilitating diseases.
Together, through awareness, support, and proactive actions, we can make a positive difference in the fight against these conditions.
Stay tuned for the follow-up article, where we will discuss :
Why it is challenging to treat NDs ? and
Most importantly, talk about science-backed tips and techniques which can be easily assimilated into lifestyle and help us to delay the onset or progression of NDs.
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