ageing and disease

Question 1

appreciate the relationship between ageing and lifespan

Answer 1

• lifespan varies across species, different genomes influence longevity
• some species like the naked mole rat, exhibit no increase in mortality rate with age

factors influencing lifespan:
- improved nutrition, sanitation and healthcare systems( vaccines, antibiotics)
- genetic factors that explain the lower mortality in extreme old age

Question 2

what is meant by ageing in biology and the key terms associated with it

Answer 2

the time related detereioration of the physiological functions necessary for fertility and survival.

longevity = how long an organism lives
senescence = age related functional decline
disease markers = conditions linked to ageing such as cancer
unrepaired damage = ageing results from the accumulation of damage that the body cannot fully repair

Question 3

the human mortality phases

Answer 3

mortality = the probablity of death in a given period of time.

1. high mortality in infancy
2. low mortality until mid life (~60 years)
3. increased mortality from mid life to old age (longer midlife)
4. reduced mortality in extreme old age

Question 4

how aging contributes to diseases like diabetes, cancer, and neurodegeneration

Answer 4

cancer:
- cases rise with age
- more women having it earlier in life and more males having it later in life
- growth of cancer rates slow in very old age

heart disease:
more common in men than women, but strongly related to ageing

demetia:
asscoated with ageing

Question 5

research methods for ageing and genetics

Answer 5

1. genetic linkage studies = identifying single gene causes of premature ageing
2. genome wide association studies(GWAS) = explore polygenic contributions, linking shared traits across age-related diseases.

Question 6

progeroid syndromes

Answer 6

= genetic disorders mimicking accelerated ageing that make individuals appear older than what they actually are

types:
segmental progeria: multiple tissues affected, autosomal recessive such as Werner syndrome and Cockayne syndrome.

unimodal progeria: single tissue primarily affected, autosomal dominant such as Alzeheimers and Parkinsons

• accelerated ageing in these syndromes mirrors natural ageing processes
• Suggests molecular defects in these conditions contribute to general aging.

Question 7

the main molecular hallmarks of ageing

Answer 7

1. genome integrity
   - loss of DNA integrity and mutations are central to ageing
   - p53 is a key regulator that activates defense mechanisms to repair damage
   - cells that cannot repair damage enter senescence, to prevent dangerous mutations but this contributes to ageing.
2. telomere shortening
   - telomeres protect chromosomes but shorten with each cell division, eventually causing cell death or senescence.
   - the hayflick limit refers to the number of times a cell can divide before telomere shortening leads to senescence.
3. cellular senescence
   - A protective, irreversible arrest in the cell cycle, triggered by factors like DNA damage and telomere loss.
   Senescent cells accumulate over time and contribute to aging by depleting stem cells and impairing tissue function.
4. dysregulated insulin signalling
   - insulin siganlling is involved in metabolism and longevity.
   - Reduced insulin signaling, especially in organisms like C. elegans, extends lifespan by activating certain longevity pathways

Question 8

loss of geenome integrity and DNA damage repair mechanisms

Answer 8

Aging results in the accumulation of DNA damage due to both intrinsic (e.g., reactive oxygen species) and extrinsic factors (e.g., UV radiation).

This damage is typically repaired by processes such as base excision repair and nucleotide excision repair, but over time, these systems become less efficient.

p53:
Known as the guardian of the genome, p53 helps detect DNA damage and induce cellular senescence or apoptosis to prevent cancerous growth.
Mutations in p53(inactivated) are found in 50% of human cancers, highlighting its role in genome stability.

Question 9

cellular senescence and its role in ageing

Answer 9

• cells age and stop dividing, but they do not die often triggered by DNA damage, telomere shortening and cellular stress.
• While it protects against cancer by halting the proliferation of damaged cells, the accumulation of senescent cells contributes to aging and age-related diseases.
• The build-up of senescent cells leads to tissue dysfunction, stem cell depletion, and increased inflammation

Question 10

relationship between insulin signalling and longevity

Answer 10

In organisms such as C. elegans, mutation in genes like age-1 extend the lifespan by altering insulin signalling

• insulin and insulin growth factor-1 are crucial for nutrient sensing, glucose uptake and fat storage.
• reduced insulin signalling leads to a longer lifespan in organisms with a daf-16 in C. elegans.

Mutations that impair insulin signaling increase lifespan and promote stress resistance.

Question 11

the role of animal models in investigating ageing

Answer 11

C. elegans:
- A model organism for studying aging, especially the effects of insulin signaling. Mutations in age-1 and daf-23 extend lifespan by reducing insulin signaling, highlighting the link between metabolism and longevity.

mammalian animals:
Studies in mammals (e.g., mice) show that insulin signaling and caloric restriction can extend lifespan by improving metabolic efficiency and reducing age-related diseases.

telomerase and ageing:
studies using telomerase in animal models have shown that restoring telomerase activity can prevent telomere shortening and delay aging in some contexts.

Question 12

What is Dauer formation in C. elegans, and how is it regulated by insulin signaling?

Answer 12

Dauer formation is a stress-resistant, developmental stage in C. elegans where larvae enter stasis under harsh conditions.

Insulin signaling regulates Dauer formation; reduced insulin signaling promotes longevity by maintaining a longer developmental stage.

Question 13

proteostasis and its key components

Answer 13

proteostasis = the maintanence of a functional proteome throughproper protein synthesis, folding and degradation.

proteostasis imbalances in ageing:
- insufficient clearance of misfolded proteins
- misregulated transcription
- loss of molecular chaperones (sHSP)
- accumulation of toxic misfolded oligomers and insoluble aggregates

consequences:
- damaged proteins accumulate due to impaired removal mechanisms
- creates a feedback loop, increasing damage.

Question 14

protein aggregation and neurodegeneration

Answer 14

protein aggregation = misfolded proteins cluster together, forming aggregates that accumulate in cells.
- common in late onset neurodegenerative diseases

Alzheimer’s:
two main hallmarks:
1. Amyloid plaques -> extracellular deposits of amyloid beta (AB) peptides (amyloid plaques)
2. Neurofibillary tangles(NFTs) -> intracellular aggregates of hyperphosphorylated Tau protein

Question 15

the genetics of Alzheimer’s disease

Answer 15

two types:
1. famillial AD
- early onset <65 years
- autosomal dominant mutations in APP(gene found on chromosome 21) and presenilin

2. Sporadic AD
   - late onset >65 years
   - strongly associated with ApoE4 genotype, other SNP’s with minor effects.
   -

Question 16

Describe the Molecular Basis for Neurodegeneration in Early-Onset Familial AD

Answer 16

APP proteolytic processing:
proteases are enzymes that cut other proteins (a-secretase(non-amyloidogenic), B-secretase and y-secretase(amyloidogenic)
- y-secretase generates amyloid beta peptides of varying lengths

gamma-secretase:
- multi protein complex( Presenilin-1 (PSEN1), nicastrin, APH-1, PEN-2.)
- it cleaves APP, and transmembrane receptors

Aβ Peptides:
Aβ42 is more aggregation-prone, forming amyloid plaques.
FAD mutations often shift the balance toward Aβ42 production.

Question 17

Tau protein and neurofibillary tangles

Answer 17

normal role = stabilizes microtubules, essential for axonal proteins transport and synaptogenesis.

In AD = Hyperphosphorylated tau forms NFTs, disrupting microtubule dynamics and neuronal function.

Question 18

cancer definition and it’s association with ageing

Answer 18

cancer = caused by abnormal cell division in an uncontrolled way.

• all cancers are genetic, but susceptibility to some cancers is familial (in family)
• peak rates occur between ages 85-89 as cancer development requires the accumulation of multiple mutations and DNA damage over long periods of time.
• 5-6 independent mutations are typically required to cause cancer, contributing to it’s multi stage development ( initiation, promotion, progression and metastasis)

Question 19

the role of proto-oncogenes in cancer

Answer 19

proto- oncogene = normal cellular genes involved in cell growth/ cell division.
- when proto-oncognes are mutated or are over expressed they become oncogenes.
- oncogenes = result in a dominant, gain of function phenotype. (only needs one copy to be mutated)

mechanisms of proto -> oncogenes;
1. point mutations
- hyperactive proteins proliferate and grow uncontrollably (Ras mutations)

2. gene amplification
   - normal proteins are overproduced
3. chromosomal rearrangement
   - the breaking and re-joining of different chromosomes cause overexpression or production of fusion proteins

Question 20

role of tumour suppressor genes in cancer

Answer 20

tumour suppressor genes = loss of a gene that normally suppresses or controls cell division
- mutations in these genes cause loss of function, requiring both copies to be mutated (recessive)

examples:
p53: Regulates DNA repair, apoptosis, and the cell cycle. Mutated in ~50% of human cancers.

RB (Retinoblastoma protein): Controls cell cycle progression from G1 to S phase.

Question 21

Explain why some cancers, for example, retinoblastoma, occur in children.

Answer 21

= retinoblastoma occurs due to mutations in the RB gene, which is critical for regulating cell division in retina cells.

Knudson’s two hit hypothesis;
- the first mutation in inherited (germeline)
- the second mutation is somatic

Children inherit one mutated RB allele and are predisposed to developing the disease with just one additional mutation.

Question 22

p53 function in cancer cells

Answer 22

Normal: Activated in response to DNA damage, halts cell cycle, and triggers repair or apoptosis.

Mutated: Loses the ability to regulate cell division, allowing mutations to accumulate. (absence)

Question 23

BRCA1/BRCA2 in Breast Cancer:

Answer 23

BRCA1/BRCA2 = tumour suppressor genes involved in DNA repair.
- mutations lead to defective repair and accumulations of mutations, increasing the risk of early onset breast cancer.
- hereditary breast cancers account for 10% of cases.

Question 24

the two types of cancer

Answer 24

sporadic = more frequent, no hereditary cause
familial = less frequent, hereditary

Question 25

What is the role of the RB protein in the cell cycle?

Answer 25

RB controls progression from the G1 to S phase by regulating E2F, a transcription factor for DNA replication genes.

Question 26

the 5 original hallmarks of cancer (2000)

Answer 26

1. sustaining proliferative signalling
   - cancer cells override normal growth regulation, leading to continuous cell division.
2. evading growth suppressors
   - tumour suppressor genes such as p53 are inactivated, leading to uncontrolled cell growth
3. enabling replicative immortality
   - cancer cells maintain telomere length through telomerase(in normal cells they shorten), enabling continuous division, no apoptosis and abnormal cellular ageing.
4. inducing angiogenesis
   - cancer cells stimulate the formation of new blood vessels(pro angiogenic factors) that supply endless nutrients, this allows tumours to grow beyond a small size.
5. activating invasion and metastasis
   - Cancer cells can invade neighboring tissues and spread to other body parts via the bloodstream (intravasation) and form secondary tumors (extravasation).

Question 27

updated hallmarks (2011)

Answer 27

1. deregulating cellular energetics
   - how ATP is produced within cancer cells
2. genome instability and mutation
   - Increased mutations, especially in genes related to DNA repair.
3. avoiding immune destruction
   - Cancer cells evade immune surveillance to survive and spread.
4. tumour promoting inflammation
   - the tumor environment may foster cancer growth and spread.

Question 28

cancer treatment approaches

Answer 28

conventional:
- surgery (removing tissue tumour)
- radiation therapy (targetting cancer cells to destroy them)
- chemotherapy( using drugs to kill cells)

alternative therapies:
- gene therapy (modifying genes)
- Antiangiogenesis: Targeting blood vessel formation to starve tumors.
- targeted chemotherapy (specific molecules)

Question 29

the physical and social impact of age related diseases relatig to the musculoskeletal system

Answer 29

physical;
- chronic pain, reduced mobility, risk of fractures
- Sarcopenia, osteoarthritis, and osteoporosis can significantly diminish quality of life.

social:
- financial burdens(treatment, loss of productivity)
- psychological effects

Question 30

Osteoporosis

Answer 30

= the loss in bone density, diagnosed when bone mass in 2.5SD below the mean peak bone mass.

osteopenia = less severe bone loss (1-2.5SD below)

• often identified after fractures
• peak bone mass is reached around 20-30

risk factors;
1. age = imbalance in bone remodelling (osteoblast < osteoclast activity, more bone broken down than built up)

2. physical activity = regular loading (weight lifting) promotes bone density, declines with age.
3. calcium and vitamin D = calcium absorption decreases with age, Vitamin D deficiency lowers calcium uptake, affecting bone strength.
4. hormones = postmenopausal women lose bone due to decreased estrogen, Changes in calcitonin, parathyroid hormone, and glucocorticoids exacerbate loss.
5. genetic factors = up to 40% of bone density variation is genetic; links to sarcopenia and osteoarthritis.

Question 31

osteoarthritis

Answer 31

= degenerration of synovial joints, leading to pain and stiffness.

causes:
cartilage thinning, reduced water content, and protein matrix changes (collagen)

prevalence:
- affects over 50% of people over 75
- higher prevalence in women

risk factors:
obesity, genetics, manual labour, repetitive tasks

Question 32

sarcopenia

Answer 32

= loss of skeletal muscle mass and function, (equivalent of osteoporosis for the muscle)

• up to 50% loss of muscle mass by age 70
• Fibrous and adipose tissue infiltrate muscles; satellite cell numbers reduce.

risk factors:
- insulin resistance, fatifue, falls and increased mortality

Question 33

cosmetic and physical changes in ageing

Answer 33

• dermal thinning reduces collagen and elasticity and smaller fat cells lead to sagging and wrinkly skin.
• reduced function of sebaceous and sweat glands contribute to dry skin.

botox = works by inhibiting the release of acetylcholine, preventing muscle contractions and temporarily reducing wrinkling.

minoxidil = used for hair regrowth by improving blood flow to hair follicles

Pattern baldness and increased hair growth in areas like the eyebrows, nostrils, and ears occur with ageing.

Question 34

age related changes in the cardiovascular system

Answer 34

1. heart muscle changes
   - thickening of the left ventricular wall and increased collagen causes the heart ot become less efficeint, reducing oxygen supply to the body
   - fatigue and lower exercise tolerance
   - reduced responsiveness to exercise and slower recovery rates after activity
2. valve changes
   - increased thickness and decreased flexabillity in heart valves leading to calcification in aortic and mitral valves.
   - can result in heart murmurs and hypertrophy (thickening) over time
   - valve replacement is a common treatment for severe valve dysfunction.
3. changes in the conduction system
   - decline in pacemaker cells and fibrous tissue infiltration can lead to arrhythmias(especially after an ischaemic event, lack of blood flow) and sinus bradycardia(slow heart rate)
4. contraction and excitation coupling
   - In the elderly, the rate and force of heart contraction may decrease, leading to heart failure.
   - (calcium influx) becomes less efficient, reducing heart contractility. -> heart failure

Question 35

heart failure and treatment

Answer 35

• reduced cardiac output leads to symptoms such as fatigue, cyanosis, peripheral and pulmonary odema.
• treatments work on making the heart work more efficiently or inloading the heart (reducing blood volume to the heart)

odema:
= is caused by an imbalance in fluid transport which leads to fluid accumulation in tissues and cavities(lung, leg)

drugs:
1. nitrates - reduces blood return to the heart

2. positive inotropic agents - enhanves calcium influx, making the heart contract more efficiently
3. ACE inhibitors - lower blood pressure and reduce water retention by the kidneys

Question 36

what prevents and induces pulmnoanry odema?

Answer 36

prevents:
- - Pulmonary Hydrostatic pressures are much lower than systemic pressure
- - Therefore have a net fluid transfer at both ends

induces:
- Higher pulmonary hydrostatic pressures

Question 37

blood pressure changes with ageing

Answer 37

• systolic blood pressure rises disproportionally to diastolic pressure, this can lead to isolated systolic hypertension, particulary in people over 50.
• Age-related changes in the elasticity of arteries (e.g., reduced elastin) contribute to increased systolic pressure.
• pulse pressure (systolic-diastolic) is a risk indicator for CVD.

Question 38

hypertension

Answer 38

• primary hypertension (90%) is multifactorial with contributors such as smoking, obesity, diet, lack of exercise and genetics.
• secondary hypertension (<10%) is caused by other health conditions.

Treatment includes lifestyle changes and various medications (e.g., beta blockers, ACE inhibitors, calcium channel blockers).

Question 39

ageing changes in the aorta

Answer 39

• dilated, elongated, rigid
• calcifications may develop
• decreased elastin, increased collagen = calcifications
• increased stiffness
• decreased compliance
• artery wall can weaken in specific area to cause an aneurysm

Question 40

atherosclerosis

Answer 40

= a chronic inflammatory disease affecting large and medium sized arteries, starting with fatty streaks and progressing to raised lesions.

Fibrous cap forms over lesions, and inflammation can cause plaque rupture and blood clots.

• treatments include: lipid lowering drugs, antiplatet drugs, drugs to lower blood pressure and stenting procedures.

Question 41

function, structure and organisation of the endocrine system

Answer 41

function = the endocrine system regulates critical processes such as metabolsim, growth, development, reproduction and immune function by releasing hormones from specialized glands. These include the hypothalumus, thyroid gland, pituatary gland and adrenal glands.

Question 42

hormones

Answer 42

= chemical signalling molecule that travels through the blood to target cells. They have effects on different organs and tissues by binding to specific receptors.

types of hormones:

1. water soluble hormones:
   - eg peptide hormones
   - act through secondary messengers and modify target proteins
   - hydrophillic
   - primarily dissolve in the plasma
2. lipid soluble hormones
   - hydrophobic
   - eg steroid hormones
   - affect gene transcription and are carried by plasma proteins

Question 43

the pituatary gland

Answer 43

• controls many other endocrine glands and their function
• hypothalamus regulates activity of pituatary gland

structure:
posterior pituatary = stores and releases hormones such as andiuretic hormone (ADH) and oxytocin, produced in the hypothalamus.

anterior pituatary = produces hormones like growth hormone(GH), thyroid stimulating hormone (TSH) AND FSH, and is made up of epithelial cells.

Question 44

negative feedback in the hypothalamic pituitary axis

Answer 44

The hypothalamus secretes releasing hormones that stimulate the anterior pituitary to release stimulating hormones. These hormones target peripheral glands (e.g., thyroid, adrenal glands).

example:
Thyrotropin-Releasing Hormone (TRH) from the hypothalamus stimulates the release of TSH from the pituitary, which triggers the thyroid to produce T3 and T4.
High levels of T3 and T4 exert negative feedback on the hypothalamus and pituitary to reduce TRH and TSH secretion, maintaining hormonal balance.

Question 45

Regulation of the synthesis and secretion of anterior pituatary

Answer 45

1. neurons in the hypothalamus release releasing or inhibiting hormones
2. these hormones travel in a portal blood system to the anterior pituatary gland
3. for releasing hormones -> ant pituatary secretes hormones into blood, where it travels to its target and produces it’s response
4. for inhibiting hormone -> ant pituatary stops hormone secretion which in turn has a knock on affect on target tissue

Question 46

effects of ageing on the endocrine system

Answer 46

• hormone levels tend to decline with age, target cells may become less responsive to these hormones.

somatopause = decreased production of growth hormone(GH) and insulin-like growth factor 1(ILGF-1) which results in increased body fat, reduced muscle mass and lower bone density.
- exercise can slow the decline of GH

hypothyroidism = reduced thyroid hormone production(T3), leading to slower metabolism and weight gain.

Impact of Chronic Disease: Conditions like liver and kidney disease can affect the metabolism and excretion of hormones, further altering endocrine function.

Question 47

endocrine changes during the menopause

Answer 47

• decline in ovarian function and estrogen production.

ovarian follicle depletion = menoppause occurs when the ovaries have fewer than 1,000 follicles left, there are no grandulosa cells left to produce oestrogen.

• decreased oestrogen leads to reduced negative feedback on the hypothalamus and pituatary leading to increased secretion of FSH and LH.

Question 48

hormone replacement therapy (HRT)

Answer 48

• should be used to relieve menopausal symptoms

types:
Estrogen + Progesterone: For women with an intact uterus to prevent endometrial hyperplasia.
Estrogen only: For women who have had a hysterectomy.

benefits:
- reduced menopausal symptoms
- maintains bone density
- maintain vascular health and reduce CDV risks

risks;
slight increased risk of breast and ovarian cancer with prolonged use

Question 49

Non-Pharmacological Management of Menopausal Symptoms

Answer 49

• nutrition
• cognitive behavioural therapy
• exercise
• stop smoking
• anti depressants if needed for mood

Question 50

Alzheimers disease symptoms

Answer 50

moderate stage:
Difficulty with daily tasks.
Memory loss of current events or personal life events.
Poor judgment and inability to perceive danger.
Sundowning (confusion in the late afternoon or night).
Confused speech.
Delusions and hallucinations.
Mood changes.
Withdrawal from social activities.

late stage:
Inability to recognize family members.
Loss of ability to perform daily activities (eating, dressing, bathing).
Loss of communication abilities.
Loss of bladder and bowel control.
Difficulty swallowing.

Question 51

Alzheimers disease pathology

Answer 51

Amyloid Beta (Aβ):
Amyloid plaques are dense deposits of Aβ protein and cellular material that accumulate outside neurons (extracellular).
Aβ40 and Aβ42 are the two primary forms of amyloid peptides, with Aβ42 being more toxic.

Tau (P-tau):
Neurofibrillary tangles (NFTs) are twisted fibers of hyperphosphorylated tau protein that build up inside neurons (intracellular).
These misfolded tau proteins disrupt normal neuron function.

Question 52

the amyloid cascade hypothesis

Answer 52

• suggests that the accumulation of amyloid plaques is the central event in Alzheimer’s disease progression.

Amyloid Precursor Protein (APP) is cleaved to produce Aβ peptides. Overproduction or impaired clearance of Aβ leads to plaque formation.
The plaques trigger inflammation and tau pathology, resulting in neurodegeneration.

• therapies targeting amyloid plaques have been largely unsuccessful in clinical trials

Question 53

diagnostics and biomarkers in alzheimers disease

Answer 53

Probable Alzheimer’s Disease:
Clinical diagnosis is based on progressive memory loss, cognitive decline (e.g., aphasia, apraxia, agnosia), and impaired daily life activities.
Imaging may show brain atrophy.

Definitive Alzheimer’s Disease:
Histopathological confirmation is required, typically post-mortem, showing amyloid plaques and neurofibrillary tangles.

Biomarkers:
Amyloid PET Scan: Uses 11C-PiB radiotracer to detect amyloid plaques.

CSF Analysis: Low levels of Aβ42 and elevated levels of tau (especially phosphorylated tau) in cerebrospinal fluid (CSF) are indicative of Alzheimer’s.

FDG-PET: Measures glucose metabolism in the brain, showing a characteristic decrease in temporo-parietal regions in Alzheimer’s.

Question 54

cholinegeric hypothesis

Answer 54

= proposes that alzheimers is associated with a deficit in acetylcholine, a neurotransmitter that is critical for memory and cognitive functions.

The nucleus basalis of Meynert (NBM) is the primary source of cortical cholinergic innervation, and degeneration in this region is a hallmark of AD.

Cholinergic therapies: Cholinesterase inhibitors (e.g., donepezil) increase acetylcholine levels and have shown symptomatic improvement, but their efficacy is limited.
Cholinergic agonists, both muscarinic and nicotinic, have not been effective in treating AD due to side effects.

Question 55

risk factors for alzheimers disease

Answer 55

Age: The risk increases with age, particularly after 65 years

Physical inactivity, poor diet, and untreated hearing loss are associated with an increased risk of developing AD

Cardiovascular conditions, diabetes, and high cholesterol can also contribute to the development of AD.

traumatic brain injury, hypertension, smoking,

Question 56

parkinsons disease symptoms

Answer 56

Non-motor Symptoms (Prodromal Phase, onset):
Cognitive impairment (e.g., dementia, hallucinations).
Mood disorders (e.g., depression).
Sleep disturbances (e.g., REM sleep behavior disorder).
Autonomic dysfunction (bladder issues, constipation).
Loss of sense of smell (hyposmia) and pain.

Motor Symptoms:
Resting Tremor: Present at rest, disappearing with voluntary movement.
Rigidity: Muscle stiffness, causing pain and difficulty moving.
Bradykinesia (Slowness of Movement): Slower movements in daily tasks and difficulty initiating movement.
Postural Instability: Difficulty maintaining balance, leading to falls.
Freezing of Gait: Sudden inability to move, particularly when starting to walk.

Question 57

hallmarks of Parkinson’s

Answer 57

Dopamine Loss:
PD is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is part of the basal ganglia.
This results in decreased dopamine levels in the striatum, impairing motor control.

Lewy Bodies:
Intraneuronal inclusions of alpha-synuclein protein aggregates, known as Lewy bodies, are found in surviving neurons, especially in the SNpc.
Misfolded alpha-synuclein forms clumps that disrupt normal neuronal functions and contribute to neurodegeneration.

Lewy bodies: abnormal highly insoluble protein aggregates inside neurons

Question 58

Braaks hypothesis

Answer 58

Braak’s hypothesis suggests that Parkinson’s disease begins in the enteric and olfactory neurons and spreads to the brain through the vagal nerve and olfactory tract.

Symptoms may start with non-motor features like anosmia (loss of smell) and gastrointestinal issues, progressing to motor symptoms as the disease advances

Question 59

molecular events underlying Parkinsons

Answer 59

PD involves multiple molecular pathways:
Mitochondrial dysfunction: Mitochondria in dopaminergic neurons are damaged, leading to energy deficits.

Oxidative stress: Excessive production of reactive oxygen species (ROS) damages cells and proteins.

Excitotoxicity: Overactivation of glutamate receptors contributes to neuronal injury.

Protein Misfolding: Misfolded proteins like alpha-synuclein aggregate into Lewy bodies, further damaging neurons.

Inflammation: Chronic neuroinflammation exacerbates neuronal damage.