1answer.
Ask question
Login Signup
Ask question
All categories
  • English
  • Mathematics
  • Social Studies
  • Business
  • History
  • Health
  • Geography
  • Biology
  • Physics
  • Chemistry
  • Computers and Technology
  • Arts
  • World Languages
  • Spanish
  • French
  • German
  • Advanced Placement (AP)
  • SAT
  • Medicine
  • Law
  • Engineering
djverab [1.8K]
2 years ago
8

FIRST RIGHT ANSWER GETS BRAINLIEST

Biology
1 answer:
Andrew [12]2 years ago
8 0

Explanation:

Genetics has taught us a great deal about disorders in which the underlying cause is complex and, thus, often relegated to the catch all “sporadic” diseases. However, the gap between identifying genes and understanding their pathogenic pathways remains enormous. In this context, the new study by Mazzulli et al. (2011) in the current issue of Cell uncovers a tractable biochemical relationship between two complex diseases, the neurodegenerative disorder Parkinson's disease and the lysosomal disorder Gaucher disease, in which lipids accumulate in central organs.

Parkinson's disease is characterized by two pathological features. First, neurons die in regions of the brain, which control the normal fluidity of movement. This leads to the clinical picture of tremor, stiffness, slowness, and difficulties with posture. Second, proteins and lipids accumulate into structures, called Lewy bodies, inside surviving neurons (Gai et al., 2000). The synaptic protein α-synuclein is one key component of Lewy bodies, and variations in its gene, SNCA, are associated with inherited and sporadic Parkinson's disease (Hardy, 2010). When present in Lewy bodies, α-synuclein is aggregated; however, it is unclear which species causes cell death, the aggregated form or some intermediate in the aggregation pathway, such as soluble oligomers.

Gaucher disease is an autosomal recessive disorder caused by mutations in the GBA gene, which encodes the enzyme glucocerebrosidase (GCase). Parents and grandparents of patients with Gaucher disease have unusually high rates of Parkinson's disease, suggesting that these mutations are risk factors for Parkinson's disease (Velayati et al., 2010). Although mutations underlying Gaucher disease are loss of function, patients with Parkinson's disease always carry one wild-type GBA allele and thus possess at least 50% of normal enzyme function. Furthermore, there is no obvious correlation between the type of GBA mutation (i.e., completely inactive or one with some residual enzyme activity) and the risk of Parkinson's disease (Velayati et al., 2010). Thus, the genetic mechanism by which GBA mutations promote Parkinson's disease is still not clear.

GCase catalyzes the conversion of glucocerebroside to glucose and ceramide inside the lysosome. One possible link between GCase function and Parkinson's disease risk is α-synuclein. The main degradation pathway of α-synuclein is via lysosomal processing, and GCase interacts with α-synuclein in acidic environments, such as the lumen of the lysosome (Yap et al., 2011). Interestingly, α-synuclein has been shown to inhibit vesicle transport between the endoplasmic reticulum (ER) and the Golgi apparatus, the main trafficking route for GCase to reach the lysosome. Thus, increased expression of α-synuclein should decrease levels of GCase in lysosomes. As an aside, mutant α-synuclein can inhibit chaperone-mediated autophagy, a process by which some substrates are imported into and degraded by the lysosome . Therefore, lysosomal dysfunction could increase α-synuclein levels, and α-synuclein could inhibit lysosomal function in multiple ways.

Indeed, the central idea in the paper by Mazzulli et al. is that this exact type of positive feedback loop occurs in Parkinson's disease patients carrying GBA mutations. To model the loss of enzyme function seen in these patients, the authors decrease the expression of GBA in mouse neurons to ∼50% of control conditions. Over a few days in culture, the neurons loose lysosomal turnover of long-lived proteins, including α-synuclein. The author observe this phenotype in primary neurons and in neurons reprogrammed from induced pluripotent stem cells (iPSCs), with the latter having both copies of GBA mutated, as found in neurons from patients with Gaucher disease.

The authors then characterize the formation of α-synuclein oligomers in cells, in mice, and in brains from people who had mutations in GBA. Soluble oligomers are found in neuronopathic forms of Gaucher disease, as well as Parkinson's disease patients heterozygous for GBA mutations. This observation suggests that the emergence of oligomers is not correlated with Lewy bodies but rather is a more fundamental consequence of GBA mutations. Mazzulli and colleagues also show that expression of α-synuclein impacts the trafficking of GCase from the ER-golgi to the lysosome, indicating that α-synuclein affects lysosomes irrespective of the presence of GBA mutations.

Simplistically, the data by Mazzulli and colleagues suggest the following model: a rise in α-synuclein levels through mutation, response to stress, or neuronal maturation (Li et al., 2004) inhibits the normal negative feedback loop of degradation by the lysosome, leading to more α-synuclein and more inhibition . Then the system would transition from one stable state to a second one that is self-sustaining, unless another pathway intervenes to stop it.

You might be interested in
Pollen is carried from one flowering plant to another by
Anika [276]

Pollen can be carried to multiple flowering plants by animals called pollinators, which can be bees, birds, spiders, or even small mammals!

6 0
3 years ago
Que tipo de relación existe cuando una especie que utiliza a otra como vivienda
Ierofanga [76]
Talk in English I don’t understand
4 0
3 years ago
Cultural evolution and biological evolution are similar in some ways. Important distinctions between them include:
Alenkasestr [34]

Answer:

i would go with b

Explanation:

Both are based on variation, heredity and selection, but how these appear and work differ. Biological evolution is unconscious, opportunistic and not goal-directed, while cultural evolution is conscious, at best planned, and can have a goal.

8 0
2 years ago
Explain what happens to the ecosystem and environment of an area if the suns raid iron is reduced
Alisiya [41]
I think the organisms in that ecosystem would most likely have an problem in there ecosystem because if any animal adapted to that environment they would most likely be already adapted to that environment
6 0
3 years ago
Examine the list of cell characteristics. lack nuclei have cell walls have membrane-bound organelles are smaller than eukaryotic
Mazyrski [523]

Answer:

Explanation:

Prokaryotic cells are very simple so they have:

circular chromosome

smaller than eukaryotic cells

lack nuclei

have cell walls

5 0
3 years ago
Other questions:
  • What are some non examples of a chemical reaction?
    11·1 answer
  • How do mitosis and meiosis differ in the division of genetic composition?
    13·2 answers
  • Will upvote if answered!!:
    8·1 answer
  • True or False. Earths temperature is produced because the suns energy reaches all places on earth uniformly
    8·1 answer
  • Organisms classified using a dichotomous key are based on A. physical characteristics. B. geographic area. C. behaviors. D .gene
    7·1 answer
  • What is the temperature of earths layers?
    14·2 answers
  • Reeve a, simcox e, turnbull
    5·1 answer
  • What is facilitated diffusion??
    15·1 answer
  • Match the following terms and definitions.
    6·1 answer
  • The connective tissue that surrounds and separates individual skeletal muscle fibers (cells) is called:_________
    7·1 answer
Add answer
Login
Not registered? Fast signup
Signup
Login Signup
Ask question!