1. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis are caused by the progressive loss of structure and function of neurons in the brain and spinal cord. 2. These disorders are characterized by the abnormal deposition of misfolded proteins that form plaques and tangles within neurons, leading to neuronal dysfunction and death. 3. Common symptoms across neurodegenerative disorders include cognitive decline, psychiatric symptoms like depression, and movement problems; the specific manifestations depend on the areas of the brain affected.

1. NEURODEGENERATIVE DISORDERS
SYED MUDABIR AHMAD

2. • Neuroscience, also known as Neural Science, is the study of how the
nervous system develops, its structure, and what it does.
• Brain, the controlling unit of the body comprise of billions of cells
(neurons) which form the communication centre (nervous system).
• Neurons: Specialised cells, convey sensory information into the brain,
transmit commands from the brain to control organs and muscles, thought,
feeling and movement.

3.  The progressive loss of nerve structure and function is called as neurodegeneration,
which leads to the loss of cognitive abilities such as memory and decision making.
 Neurons, the building blocks of the nervous system which includes the brain and
spinal cord, normally doesn’t reproduce or replace themselves when damaged or die.
 Neurodegeneration is a key aspect of a large number of diseases that come under the
umbrella of “neurodegenerative diseases.” Of these different disorders, the most
notable being Alzheimer’s disease, Parkinson’s disease and Huntington disease.
 Although these three diseases manifest with different clinical features, the disease
processes at the cellular level appear to be similar.

4.  Alzheimer’s disease is a progressive
neurodegenerative disease that mostly
affects patients in their later stage of life.
 Typical symptoms of Alzheimer’s disease
are loss of cognitive functions including
emotion, learning and memory
processing skills leading to dementia.
 About 70% of the risk is believed to
be genetic with many genes involved.
Other risk factors include a history
of head injuries, depression,
or hypertension.

5.  The pathological impression of
Alzheimer’s disease can be characterised
by the deposition of amyloid-beta (Aβ)
protein plaques in the brain parenchyma
and accumulation of tau proteins within
neurons.
 These protein plaques interfere with
synaptic transmission and neuron-neuron
communication leading to neuronal death.
 tau proteins within neurons form tangles
and block transportation of nutrients or
other vital cellular factors throughout the
cell which becomes reason for cell death in
Alzheimer’s disease .

6. Symptoms

7.  Parkinson’s disease is typically considered a chronic, progressive neurodegenerative
movement disorder.
 Parkinson’s primarily cause death of the vital nerve cells in the area of brain called
substantia nigra.
 Some of these dying neurons produce dopamine which acts as messenger and sends
message to the part of the brain that controls the movement and coordination.
 As the Parkinson’s disease progresses the amount of dopamine produced from the
brain decreases, leading a person unable to control movement normally.

8.  Further, proteosomal and lysosomal
system dysfunction and reduction in
mitochondrial activity due to
genetic mutations also cause cell
death.
 Activated neurons over expressing
some proteins lead to early
activation of microglia and release
of various inflammatory mediators
such as IL-1, IL-6 and TNF-α and
also the reactive oxygen/nitric oxide
species and prostaglandins enhance
oxidative stress and trigger cell-
death pathways

9. Symptoms

10.  Multiple sclerosis is a chronic
neuroinflammatory, progressive,
degenerative disorder of the CNS
characterized by demyelination of
nerve fibers of the brain and spinal
cord affecting people mostly between
of 20 and 40.
 Initially triggered by a virus in
genetically susceptible individuals
 Subsequent antigen-antibody reaction
leads to demyelination of axons i.e;
autoimmunity .

11.  Fatigue
 Depression
 Memory change
 Pain
 Spasticity
 Tremor
 Double Vision/Vision Loss
 Weakness
 Dizziness/Unsteadiness
 Numbness/Tingling
 Ataxia
 Speech disturbance
 Bladder/Bowel/Sexual
dysfunction
Symptoms

12.  Huntington’s disease is a rapidly progressive neurodegenerative disease that leads to
dementia.
 Typically presents with alterations in mood as well as a change in character, defects
in memory and attention.
 Progresses to a movement disorder consisting of involuntary and rapid motions.
 Usually not recognized until the patient is in their early 30’s.
 There is a 50% chance that a child whose parent has Huntington's will have the
disease.

13.  It is caused by an autosomal dominant
mutation on either of an individual's two
copies of a gene called Huntingtin,
which means any child of an affected
parent has a 50% risk of inheriting the
disease
 The faulty gene that causes Huntington's
disease is found on chromosome number
four.
 The normal copy of the gene produces a
protein called huntingtin, but the faulty
gene contains an abnormal region of
what are called CAG repeats. This area
is larger than normal and produces a
mutant form of huntingtin.

15.  The expanded ployglutamine region of
the pathological form of the protein
causes impairment of the ubiquitin-
proteasome system.
 This means that the dysfunctional protein
is not removed and destroyed as it should
be.
 Cells in parts of the brain- specifically,
the basal ganglia and parts of the
cortex are very sensitive to the effects of
the abnormal huntingtin. This makes
them function poorly and eventually die.

16.  The accumulation of the abnormal protein is believed to be what causes neurological
changes.
 The excess of the mutated protein interferes with neurotransmitters.
 The brain normally sends messages through the basal ganglia and cortex to control
movement and thinking, as well as motivation. If this part of the brain is damaged, it
causes problems with control of movement, behaviour and thinking.
 It's still unclear exactly how abnormal huntingtin affects the brain cells and why some
are more sensitive than others.
 Lack of physical activity, dietary problems, and eating and swallowing problems can
cause constipation, weight loss and depression.

17. • Choreic movements
• Twitching
• Balance problems
• Tracking problems
• Rigidity and dystonia
1. Movement
symptoms

18. 2. Cognitive
 As Huntington's disease progresses, the ability to concentrate becomes more
difficult
 May have difficulty driving, keeping track of things, making decisions, answering
questions, and may lose the ability to recognize familiar objects.
 Over time judgment, memory, and other cognitive functions begin to deteriorate
into dementia.
18

19. 3. Psychiatric
 Early psychiatric symptoms of Huntington's disease are subtle, varied, and easily
overlooked or misinterpreted
 Depression is the most common psychiatric symptom and often develops early in
the course of the disease. Signs of depression include:
- Hostility/irritability
- Inability to take pleasure in life (anhedonia)
-Lack of energy
- Hallucinations
19

20.  A major hallmark of neurodegenerative diseases is the abnormal deposition of
aggregates of misfolded proteins (proteinopathies) that lead to cell dysfunction and
eventually cell death (Wakabayashi and Tanji, 2009).
 Imbalanced defense mechanism of antioxidants, overproduction or incorporation of
free radicals from environment to living system leads to serious functional or sensory
loss in neurodegenerative diseases (Raymund AC Roos 2010).
 The protein plaques are able to evade degradation mechanisms and initiate a series of
neurotoxic effects, including synaptic dysfunction and disruption of cellular
organelles and the cytoskeleton, enabling an inflammatory response and ultimately
leading to cell death. (Lee, Lim, and Masliah.,2011).

21.  Infiltration of lymphocytes into the CNS during neurodegenerative diseases initiate
inflammatory responses, neuronal injury and neurotoxicity in CNS (Shrestha and
Shakya 2014)
 The accumulation of protease-resistant misfolded including the ubiquitin-proteasome
system, chaperone mediated autophagy and macroautophagy and aggregated proteins
is a common mechanism underlying neurodegenerative diseases (Aaron and Yong
2015).
 Prevalence rate of dementia is tightly linked to ageing, neurodegenerative diseases
become more prevalent with age being accompanied by progressive motor and
cognitive impairment (Marina et al.,2016).
Continued…

22.  Understanding of the genetics and initial symptoms and signs
associated with neurodegeneration.
 Studying pathophysiology and identification of an accessible tissue
biomarker prior to symptom development.
 Improved tests for identifying the conditions so they can be detected
before too much neuronal loss has occurred.
 The identification of sub-populations that have the best response to
certain treatments so that the disease can be stopped as early as
possible in responsive patients.
 To find the best care for all patients and at-risk persons at this
point in time.

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Nature 3, 205-214.
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disease. Nature, 430(7000): 631-639.

24.  Michael, Flint (2006)-Mitochondrial dysfunction and oxidative stress in
neurodegenerative diseases, Nature, 443, 787-795.
 McFarland, H.F., Martin R (2007). Multiple sclerosis: A complicated
picture of autoimmunity. Nat Immunol., 8(9): 913-9.
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25. THANK YOU